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Biomedical subjects

E Wong

Publications and source records attributed to E Wong.

At least 19 recordsLinked to original sources
PubMed1996

Mechanism of selective inhibition of human prostaglandin G/H synthase-1 and -2 in intact cells.

Selective inhibitors of prostaglandin synthase-2 (PGHS-2) possess potent anti-inflammatory, antipyretic, and analgesic properties but demonstrate reduced side-effects (e.g. gastrotoxicity) when compared with nonselective inhibitors of PGHS-1 and -2. We investigated the mechanism of the differential inhibition of human PGHS-1 (hPGHS-1) and -2 (hPGHS-2) in intact cells by nonsteroidal anti-inflammatory drugs (NSAIDs) and examined factors that contribute to the increased potency of PGHS inhibitors observed in intact cells versus cell-free systems. In intact Chinese hamster ovary (CHO) cell lines stably expressing the hPGHS isozymes, both PGHS isoforms exhibited the same affinity for arachidonic acid. Exogenous and endogenous arachidonic acid were used as substrates by both CHO [hPGHS-1] and CHO [hPGHS-2] cell lines. However, differences were observed in the ability of the hPGHS isoforms to utilize endogenous arachidonic acid released intracellularly following calcium ionophore stimulation or released by human cytosolic phospholipase A2 transiently expressed in the cells. Cell-based screening of PGHS inhibitors demonstrated that the selectivities and potencies of PGHS inhibitors determined using intact cells are affected by substrate concentration and differ from that determined in cell-free microsomal or purified enzyme preparations of PGHS isozymes. The mechanism of inhibition of PGHS isozymes by NSAIDs in intact cells involved difference in their time-dependent inhibition. Indomethacin displayed time-dependent inhibition of cellular hPGHS-1 and -2. In contrast, the selective PGHS-2 inhibitor NS-398 exhibited time-independent inhibition of hPGHS-1 but time-dependent inhibition of hPGHS-2 in intact cells. Reversible inhibition of cellular CHO [hPGHS-1] and CHO [hPGHS-2] was observed with the nonselective NSAIDs ibuprofen and indomethacin, whereas inhibition by the selective PGHS-2 inhibitor DuP-697 was reversible against hPGHS-1 but irreversible against hPGHS-2.

Animals↗
PubMed1996

Effect of oral estradiol on Lp(a) and other lipoproteins in postmenopausal women. A randomized, double-blind, placebo-controlled, crossover study.

BACKGROUND: Lp(a) lipoprotein level is an independent risk factor for premature coronary artery disease and cerebrovascular accident. Concentrations of this lipoprotein tend to increase after menopause. OBJECTIVE: To determine whether oral estrogen was effective in lowering concentrations of Lp(a) lipoprotein in postmenopausal women. METHODS: A double-blind, placebo-controlled, cross-over study was conducted during a 12-month period in 100 postmenopausal women who had undergone hysterectomy. They were randomized into two groups: group 1 received oral estradiol, 2 mg/d, for the first 6 months and placebo for the second, and group 2 received these treatments in the reverse order. After completion of the crossover study, the effect of prolonged administration of oral estradiol was examined by placing all patients on active treatment and repeating the lipoprotein measurements approximately 12 months later. RESULTS: No significant differences were noted between the two groups at the commencement of the study (median concentration of Lp[a] lipoprotein, 10.78 mg/dL [range, 2.2 to 108.5 mg/dL] in group 1 and 12.74 mg/dL [range, 0.8 to 98.1 mg/dL] in group 2). Crossover analysis showed a 9.62% reduction in values of Lp(a) lipoprotein with estradiol treatment compared with placebo during 12 months of treatment (P < .001). With prolonged treatment, the median concentration of Lp(a) lipoprotein for those in group 1 decreased from 8.12 mg/dL (range, 1.05 to 57.4 mg/dL) to 5.77 mg/dL (range, 0.84 to 75.39 mg/dL) (P < .001). In group 2, the median concentration decreased from 8.19 mg/dL (range, 2.52 to 99.82 mg/dL) to 7.07 mg/dL (range, 0.70 to 48.79 mg/dL), but this difference was not significant (P = .63). CONCLUSIONS: The results of this study confirm the beneficial effect of oral estradiol on the basic lipoprotein pattern and demonstrate that this treatment is effective in reducing concentrations of Lp(a) lipoprotein in postmenopausal women.

Administration, Oral↗
PubMed1996

Nitric oxide synthase in the olfactory mucosa of the larval sea lamprey (Petromyzon marinus).

The use of nitric oxide, a product of enzymatic reduction of L-arginine by nitric oxide synthase, as a modulator of processes within the olfactory mucosa was investigated in larval sea lampreys, extant fish of ancient vertebrate origin. In the present study, we demonstrated that the sea lamprey olfactory mucosa is specifically sensitive to L-arginine, that the L-arginine responses are inhibited by an inhibitor of nitric oxide synthase, N omega-nitro-L-arginine, and that nitric oxide synthase is present in olfactory receptor cells, sustentacular cells, and basal cells. Electron microscopic examination using NADPH-diaphorase histochemistry revealed intense labeling within secretory vesicles of sustentacular cells and in proximity to mitochondria within olfactory receptor cell dendrites and sustentacular cells. At the base of the olfactory epithelium, NADPH-diaphorase staining was intense in the perinuclear cytoplasm of a subpopulation of basal cells, moderate in sustentacular cell foot processes, and scattered in olfactory receptor cell axons. Throughout axons in the olfactory epithelium and the lamina propria, labeling predominated in axonal profiles with mitochondria. These physiological and ultrastructural studies imply that in sea lamprey larvae, nitric oxide modulates peri-receptor events of L-arginine chemostimulation, olfactory receptor cell axonal activity, and developmental processes.

Animals↗
PubMed1996

Newly established MST-1 tumour cell line and tumour-infiltrating lymphocyte culture from a patient with soft tissue melanoma (clear cell sarcoma) and their potential applications to patient immunotherapy.

The establishment and characterisation of paired autologous tumour cell line (MST-1) and tumour-infiltrating lymphocyte (TIL) culture from a tumour mass of a 14-year-old Taiwanese girl with soft tissue melanoma are described. MST-1 cells grown in vitro were heterogeneous in morphology, ranging from floating round cells, loosely attached round/oval or elongated cells with prominent pseudopod-like processes, to well-attached spindle and elongated dendritic cells without obvious pseudopods. Immunostaining revealed that major melanoma-associated antigens, such as S100 protein, HMB-45, melanotransferrin, chondroitin sulphate proteoglycan, and the gangliosides GD2 and GD3, were consistently expressed by the tumour tissue, severe combined immunodeficiency (SCID) mouse xenograft and derived cell lines. Flow cytometric analysis of the tumour DNA content showed an index of 1.8 relative to normal peripheral blood lymphocyte DNA. Chromosome analysis revealed all cells at a hypotetraploid level with several clonal chromosome aberrations, including deletions at 10p and 12q, an addition at 12q, translocations t(1;14) and t(5;6). Electron microscopy showed melanosome structures. This observation and the expression of the major melanoma-associated antigens were all indicative of the melanocytic origin of MST-1 tumour. Interleukin-2 (IL-2) expanded TILs had the predominant CD8+ phenotype and the capacity to lyse cells of the cultured autologous tumour. The availability of the soft tissue melanoma cell line, the SCID mouse xenograft tumour system as well as autologous TILs described herein would provide useful materials for identifying T-cell-defined antigens as well as a model system for devising individualised cancer biotherapeutic strategies. This cell line can also be used for further studies aimed at uncovering the histogenesis of this rare cancer.

Adolescent↗
PubMed1995

Cytochrome P450 1A1 promoter as a genetic switch for the regulatable and physiological expression of a plasma protein in transgenic mice.

Transgenic and gene knockout techniques allow for in vivo study of the consequences of adding or subtracting specific genes. However, in some instances, such as the study of lethal mutations or of the physiological consequences of changing gene expression, turning on and off an introduced gene at will would be advantageous. We have used cytochrome p450 1A1 promoter to drive expression of the human apolipoprotein E (apoE) gene in transgenic mice. In six independent lines, robust expression of the transgene depended upon injection of the inducer beta-naphthoflavone, whereas the seventh line had high basal expression that was augmented further by the inducer. The low level of basal expression in an inducer-dependent line was confirmed upon breeding the transgene onto the hypercholesterolemic apoE-deficient background. In the basal state transgene expression was physiologically insignificant, as these mice were as hypercholesterolemic as their nontransgenic apoE-deficient littermates. When injected with the inducer, plasma cholesterol levels of the transgenic mice decreased dramatically as apoE expression was induced to yield greater than physiological levels in plasma. The inducer could pass transplacentally from an injected mother to her fetuses with concomitant induction of fetal transgene mRNA. Inducer could also pass via breast milk from an injected mother to her suckling neonatal pups, giving rise to the induction of human apoE in neonate plasma. These finding suggest a strategy to temporarily ameliorate genetic deficiencies that would otherwise lead to fetal or neonatal lethality.

Animals↗
PubMed1995

Lens epithelial cell mRNA, II. Expression of a mRNA encoding a lipid-binding protein in rat lens epithelial cells.

A lens epithelial (LE) cell cDNA clone, designated pLELBP, was isolated by subtraction-hybridization methods between a 4-week-old rat LE cell and rat lens fiber cell lambda ZAP cDNA libraries. The cDNA contained 683 bp, an ATG at bp 42, and an open reading frame (ORF) encoding a protein of 135 amino acids (aa), and a poly(A) signal at bp 641 (GenBank/EMBL accession No. U13253). Northern blot analysis showed that the lens mRNA was at a concentration that exceeded 100-fold that found in non-ocular tissues examined, except in skin it was found at levels equal to about 1/15 of the lens levels. In the retina, it was also found at about 1/15 of that present in the lens. By in situ hybridization analysis, the sense RNA was localized to the LE cells and to the glial cells of the retina, and negligibly to the lens fiber cells. Search of GenBank, EMBL and SwissProt data bases revealed that the LE cell mRNA and its aa encoded protein showed extensive sequence homology to members of the cytosolic lipid-binding protein (LBP) family. It matched to 91% in aa sequence homology to the protein encoded by ORF of mal1 cDNA, isolated from mouse skin squamous cell carcinoma [Krieg et al., J. Biol. Chem. 268 (1993) 17362-17369], and 99% in aa sequence homology to the protein encoded by ORF of rat skin LBP mRNA [Watanabe et al., Biochem. Biophys. Res. Commun. 200 (1994) 253-259]. Occurrence of high levels of mRNA for a specific LBP in the LE cells relative to other non-ocular tissues is consistent with a hypothesis that the encoded protein may be involved in several lens epithelial cell-specific mechanisms, possibly including differentiation, protective and nutritional processes.

Animals↗
PubMed1995

Localization of neutral endopeptidase in the ovine uterus and conceptus during the oestrous cycle and early pregnancy.

Neutral endopeptidase (NEP; EC 3.4.24.11), an enzyme which metabolizes several peptides (including oxytocin and endothelins) implicated in the control of uterine function, was found to be localized in the ovine uterus throughout the oestrous cycle and in the uterus and conceptus during early pregnancy, using immunohistochemical techniques. Positive NEP immunoreactivity was found in the endometrium principally in stromal cells, in the vasculature in endothelial and vascular smooth muscle cells, and also weakly in some glandular epithelial cells. In a layer of stromal fibroblasts several cells in thickness underlying the luminal epithelium, staining was much weaker than that in the deeper stromal cells throughout the period examined. NEP staining was also present in smooth muscle cells of the myometrium at all times, and was most intense in the layer of cells adjacent to the endometrium. In the conceptus, NEP immunohistochemical staining was found in uninucleate cells, but not in binucleate trophoblast cells, in epithelial cells of the allantois and amnion, and in the heart and brain of the Day-20 embryo. In ovariectomized ewes treated with oestrogen or progesterone separately or remaining untreated, immunohistochemical staining of NEP was stronger when compared with intact ewes, in caruncular and intercaruncular stroma and epithelia, in glands, in the vasculature and in myometrium. The staining was less intense in all cell types in ewes receiving oestrogen plus progesterone. The expression of NEP and its specific regionalization within the uterus indicate a mechanism by which the availability of biologically important peptides involved in the regulation of the oestrous cycle and implantation, including oxytocin and endothelin, can be controlled by regulation of their metabolism.

Animals↗
PubMed1995

A double-blind comparison of inhaled budesonide, long-acting theophylline, and their combination in treatment of nocturnal asthma.

In 61 patients with nocturnal asthma, the effects of budesonide, an inhaled steroid (Pulmicort; 200 micrograms twice daily), long-acting theophylline (Theodur; 200 mg twice daily), and their combination were compared. After a 2-week placebo run-in period, the patients were entered into double-blind, crossover periods of 3 weeks. Patients were allowed to use inhaled beta 2-agonists as required throughout the study. Morning and evening peak expiratory flow rate (PEFR) (percentage of predicted normal +/- SEM) was significantly higher during the budesonide (morning 77 +/- 1%; evening 80 +/- 1%) and combination therapy (morning 79 +/- 1%; evening 81 +/- 1%) than the theophylline treatment (morning 74 +/- 1%; evening 76 +/- 1%; P < 0.01, respectively). Significantly fewer sleep disturbances and fewer nighttime inhalations of beta 2-agonists were required during budesonide and combination therapy than theophylline treatment. No statistically significant differences were seen between combined therapy and budesonide alone. Budesonide, an inhaled steroid, was significantly better than the bronchodilator, theophylline, in controlling nocturnal asthma, but no additional improvement in efficacy was seen when the drugs were used in combination.

Administration, Inhalation↗
PubMed1995

Temporal headaches and associated symptoms relating to the styloid process and its attachments.

The styloid process is a slender spike-like bony process that is attached to the base of the skull that has been of interest to physicians for centuries. From this process is the attachment for five structures--three muscles and two ligaments are attached to it. Any of these soft tissues of the styloid process are prone to be torn due to trauma by way of detachment of the periosteum from the bone. These lesions may occur from auto accidents, falls, sports injuries, to prolonged medical or dental procedures requiring excessive mouth opening. The detachment of Sharpey's fibres results in the release of noxious chemicals such as kinins, histamines, prostaglandins, etc, which can produce a withdrawal reflex, causing muscle tension, ischaemia, spasm and pain. Pain transmission via C fibres may induce a host of autonomic responses as well. We have observed 11 common pains and symptoms that are associated with soft tissue lesions of the styloid process and stylomandibular ligament. They are (1) headaches localised in the anterior temporal fossa, (2) sore throat and difficulty swallowing in the absence of inflammation, (3) pain radiating to the temporomandibular joint and ear, (4) voice alteration, (5) dry, non-productive cough, (6) pain in the masseter muscle, (7) restricted mandibular opening or the "closed lock", (8) development of the "open lock", (9) sinusitis, congested stuffy nose or post nasal drip, (10) tinnitus, and (11) excessive lacrimation and bloodshot eyes. A few drops of local anesthetic into the styloid process and stylomandibular ligament attachment can temporarily relieve the pain and symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Headache↗
PubMed1995

Successful management of female office workers with "repetitive stress injury" or "carpal tunnel syndrome" by a new treatment modality--application of low level laser.

Female office workers with desk jobs who are incapacitated by pain and tingling in the hands and fingers are often diagnosed by physicians as "repetitive stress injury" (RSI) or "carpal tunnel syndrome" (CTS). These patients usually have poor posture with their head and neck stooped forward and shoulders rounded; upon palpation, they have pain and tenderness at the spinous processes C5-T1 and the medial angle of the scapula. In 35 such patients we focused the treatment primarily at the posterior neck area and not the wrists and hands. A low level laser (100 mW) was used and directed at the tips of the spinous processes C5-T1. The laser rapidly alleviated the pain and tingling in the arms, hands and fingers, and diminished tenderness at the involved spinous processes. Thereby, it has become apparent that many patients labelled as having RSI or CTS have predominantly cervical radicular dysfunction resulting in pain to the upper extremities which can be managed by low level laser. Successful long-term management involves treating the soft tissue lesions in the neck combined with correcting the abnormal head, neck and shoulder posture by taping, cervical collars, and clavicle harnesses as well as improved work ergonomics.

Adult↗
PubMed1994

Sera from some patients with antibody-associated paraneoplastic encephalomyelitis/sensory neuronopathy recognize the Ro-52K antigen.

Screening a small cell lung cancer cDNA library with serum from a patient with antibody-associated paraneoplastic sensory neuronopathy (Anti-Hu syndrome) resulted in the isolation of a cDNA clone encoding the Ro-52 kD antigen. The Ro-52 kD antigen is one of the major antigens recognized by the sera of patients with Sjögren's syndrome and systemic lupus erythematosus. Further investigation revealed that the sera of only a small percentage (4%) of patients with the Hu syndrome reacted with Ro-52 kD antigen. The cross-reactivity may result from a domain of high homology between Ro-52 kD and HuD antigen. These results emphasize the necessity of using recombinant antigens whenever possible when assaying for assaying for specific antibodies.

Amino Acid Sequence↗
PubMed1994

Footwear and falls: a case involving new cowboy boots.

We present a case in which footwear contributed to a fall that resulted in a severe closed head injury. The woman in this case was wearing new cowboy-style boots with 1.5-inch heels that placed her ankles at a position of 25 degrees plantar flexion. Each boot heel tapered at a 50 degrees angle at its posterior edge. A steel shank protruded 2.5 in posterior to the metatarsal head, serving as the anterior contact surface in lieu of normal metatarsal contact. The design of the boot plus the fact that she was carrying groceries, reduced her ability to regain her balance after she slipped, and she fell backward, hitting the floor with full force on the occiput. Initial computed tomography scan showed large subdural and epidural hematomas and hemorrhagic contracoup contusions. The patient developed clinical signs and symptoms of secondary brainstem injury, which was later substantiated by magnetic resonance imaging scan.

Accidental Falls↗
PubMed1994

Physical mapping of the split hand/split foot locus on chromosome 7 and implication in syndromic ectrodactyly.

Split hand/split foot (ectrodactyly; SHSF) is a human developmental malformation characterized by missing digits and claw-like extremities. An autosomal dominant form of this disorder has been mapped to 7q21.3-q22.1; the locus has been designated SHFD1. We have constructed a physical map consisting of overlapping yeast artificial chromosome clones for the entire region. Somatic cell hybrid and fluorescent in situ hybridization analyses were used to define SHSF-associated chromosomal rearrangements in twelve patients. An SHFD1 critical interval of 1.5 Mb was established by analysis of five patients with deletions. Translocation or inversion breakpoints found in six patients were mapped within 700 kb of each other in the critical region. Of note is that eight of the patients analyzed (67%) are in fact classified as having syndromic ectrodactyly. Thus, these mapping data establish a relationship between simple split hand/split foot and this more complex group of human birth defects. Finally, we have mapped DLX5, a member of the Distal-less homeobox gene family, to the SHFD1 critical interval.

Abnormalities, Multiple↗
PubMed1994

HPV-associated epithelial atypia in oral warts in HIV+ patients.

Reported are oral mucosal warts (HPV common antigen-positive) from 7 adult HIV+ patients in which there was cytologic atypia and disordered growth. Lesions were papillary, white to red in color, and were located on the lip, gingiva, palate, tongue, and buccal mucosa. Histologically, the keratinocytes in the lesions exhibited atypical features in the form of hyperchromatism and karyomegaly. Koilocytes were frequently seen in the upper level keratinocytes where HPV common antigen was identified. The dysplastic areas, which ranged from mild to severe, typically showed abrupt limiting margins. All lesions exhibited intense PCNA reactivity from basement membrane to surface. Nuclei of mid-level and basal keratinocytes of 3 specimens stained positively for p53 protein. We believe that the atypia found in these lesions represents cytologic change that has malignant potential. The subtype of the HPV in these lesions has not yet been determined.

Adult↗
PubMed1994

Ease of handling and efficacy of Bricanyl Turbuhaler in Asian asthmatic children.

Ease of handling as well as efficacy of a new terbutaline inhalation device--Bricanyl Turbuhaler--were evaluated among eighty-six Asian children with mild to moderate asthma with a mean age of 8.7 years (range 5 to 14 years) in an open, non-comparative trial. Clinical evaluations were performed on four occasions, ie at the beginning of the run-in period, at the start of the study medication, after 2 weeks of treatment and after a total of 4 weeks of treatment. Appraisal of handling technique was performed by the investigator at the start and end of treatment. Peak expiratory flow rate (PEF) was determined at each visit. Diaries were also kept throughout this time; PEF and asthma symptom scores were recorded every morning and evening. Maximum scores for inhalation technique were achieved by 73% of patients after combined written and verbal instructions at the start of the study and 99% of patients achieved this score at the end of the 4 week treatment period with Bricanyl Turbuhaler. Assessment revealed that approximately 90% of the patients considered loading, inhalation and handling of the Turbuhaler device to be easy, and 90% considered it to be effective in affording symptom relief. Improvements in PEF and reductions in asthma symptoms were observed during the Bricanyl Turbuhaler treatment, as compared to baseline values. All patients tolerated the study medication well without any serious adverse events. We concluded that this group of Asian children were able to use this new "Turbuhaler" device of terbutaline without any difficulty.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Inhalation↗
PubMed1994

Imaging white matter tracts and nuclei of the hypothalamus: an MR-anatomic comparative study.

PURPOSE: To evaluate the MR appearance of the hypothalamus and its associated white matter tracts. METHODS: Coronal and sagittal spin-echo images were obtained in cadaver brains. Gross and histologic sections were made of the cadaver brains. The size, shape, signal intensity, course, and pattern of structures in the hypothalamic region were identified in MR images by comparison with the anatomic sections. RESULTS: The mamillary bodies, paraventricular zone of hypothalamic nuclei, postcommissural fornix, mammillothalamic fasciculus, and anterior commissure were identified on the MR images. CONCLUSION: This study suggests that, with MR imaging of sufficiently high resolution, some of the tracts and nuclei in the hypothalamus may be identified.

Humans↗
PubMed1993

5-lipoxygenase-activating protein stimulates the utilization of arachidonic acid by 5-lipoxygenase.

5-Lipoxygenase (5-LO) and its activating protein (FLAP) are both required for cellular leukotriene (LT) synthesis, with 5-LO catalyzing both the synthesis of (5S)-5-hydroperoxy-6,8,11,14-eicosatetraenoic acid (5-HPETE) from arachidonic acid and the subsequent synthesis of LTA4 from 5-HPETE. We have previously expressed both human 5-LO and human FLAP to high levels in Spodoptera frugiperda (Sf9) insect cells, using recombinant baculoviruses. To study the mechanism by which FLAP activates 5-LO, we compared cellular 5-LO activity in Sf9 cells expressing this enzyme to that in Sf9 cells coexpressing FLAP and 5-LO. In this system, FLAP stimulates the utilization of arachidonic acid by 5-LO as a substrate, and increases the efficiency with which 5-LO converts 5-HPETE to LTA4. LT synthesis in cells coexpressing FLAP and 5-LO is inhibited by 3-[1-(p-chlorophenyl)-5-isopropyl-3-tert-butylthio-1H-indol-2-yl]-2,2- dimethyl-propanoic acid (MK-886), an LT biosynthesis inhibitor which specifically binds to FLAP. These studies in Sf9 cells, together with our recent demonstration that FLAP specifically binds arachidonic acid, suggests that FLAP activates 5-LO by acting as an arachidonic acid transfer protein.

5-Lipoxygenase-Activating Proteins↗