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Biomedical subjects

M Wong

Publications and source records attributed to M Wong.

At least 19 recordsLinked to original sources
PubMed1992

Incidence of ras oncogene activation in lung carcinomas in Hong Kong.

BACKGROUND: In Hong Kong, lung carcinomas contribute to the majority of cancer deaths among Chinese. Point mutational activation of ras oncogenes has been observed in several populations. The incidence of these mutations in Hong Kong lung carcinomas was investigated. METHODS: Lung resections obtained from 52 Chinese patients whose conditions were newly diagnosed as non-small cell lung cancer, paraffin sections from 29 Chinese patients with previously diagnosed adenocarcinoma of the lung, and paraffin sections from 49 squamous cell carcinomas were examined for the presence of point mutations in Ki-ras codon 12, N-ras codon 61, and Ha-ras codon 12 oncogenes by allele-specific hybridization after specific amplification of appropriate regions of the DNA using the polymerase chain reaction. RESULTS: Among the 130 lung carcinomas investigated, Ki-ras point mutations were detected in seven cases, of which six were adenocarcinomas and one a squamous cell carcinoma. No mutations were detected in the N-ras and Ha-ras codons. CONCLUSIONS: The incidence of Ki-ras codon 12 point mutational activation in Chinese patients with adenocarcinomas was 6 of 63 (9.5%). The incidence of Ki-ras 12 point mutational activation among men with lung adenocarcinomas in Hong Kong (6 of 32 patients, 18.8%) is significantly different from that in women in Hong Kong (0 of 31 patients, 0%). Although ras oncogenes are implicated as having a role in the development of lung adenocarcinomas, especially among smokers, it is clear from these data that they are not associated with the unusually high incidence of lung adenocarcinomas among women in Hong Kong.

Adenocarcinoma↗
PubMed1992

Asthma knowledge and management in primary schools in south Auckland.

AIMS: to examine the management of asthma in primary schools and the school teachers' knowledge, confidence and attitude in managing the pupils with asthma. METHODS: forty-two primary schools in south Auckland were randomly selected to participate. Questionnaires were posted out to the principals and another questionnaire was given randomly to 253 teachers from these primary schools. RESULTS: 76% of the school principals surveyed returned the questionnaire; and 66% of the school teachers surveyed returned a separate questionnaire. The average incidence of asthma reported by school principals and school teachers was 9.9% and 12.6% respectively, which suggests underreporting of the diagnosis of asthma. In 81% of the schools a questionnaire was used to identify students with asthma when they first join the school. School teachers had good basic knowledge on asthma, however 33% of teachers did not know that Ventolin (salbutamol) is for symptomatic treatment and 58% and 65% of teachers did not know that Becotide (beclomethasone) and Intal (sodium cromoglycate) are prophylactic medications. CONCLUSIONS: we suggest that primary school teachers should receive further education on asthma, especially on practical aspects of asthma management.

Albuterol↗
PubMed1992

Aggrecan core protein is expressed in membranous bone of the chick embryo. Molecular and biomechanical studies of normal and nanomelia embryos.

The recessive mutation nanomelia blocks the synthesis of a large aggregating proteoglycan (aggrecan) by avian embryo chondrocytes. Lack of aggrecan is associated with short stature, multiple morphological defects in cartilage, and embryo lethality. Bony defects have also been described, but were assumed to be a secondary consequence of the cartilage defect. However, two lines of evidence presented in this paper indicate that the aggrecan deficiency directly affects intramembranous bone. First, the morphology (i.e. projected area and shape) of certain membranous bones of nanomelia embryos was abnormal. Second, membranous bone from nanomelia embryos proved to be significantly stiffer in biomechanical tests that measured functional properties of the extracellular matrix. These findings were unexpected because intramembranous bones normally develop from mesenchyme and not from a cartilage intermediate, and they prompted a search for evidence of aggrecan expression in the bone of normal chick embryos. We report that: 1) aggrecan mRNA was identified by PCR analysis of total RNA isolated from day-13 chick embryo calvarium, 2) the PCR method successfully amplified aggrecan mRNA from primary chick embryo osteoblasts in culture, 3) in situ hybridization of membranous bone tissue sections demonstrated aggrecan expression by chick embryo osteoblasts in vivo, and 4) the aggrecan message was identified in Northern blots of calvarial mRNA probed at high stringency. The results of the molecular and biomechanical studies provide evidence that aggrecan is indeed expressed in membranous bone as well as cartilage. Altogether, these results suggest that aggrecan may contribute to the functional properties and the normal growth and development of avian membranous bone.

Aggrecans↗
PubMed1992

Reduced mRNA levels for the multidrug-resistance genes in cAMP-dependent protein kinase mutant cell lines.

We have previously shown that in Chinese hamster ovary (CHO) cells, a mutant cell line with a defective regulatory subunit (RI) for the cAMP-dependent protein kinase (Abraham et al: Mol. Cell. Biol., 7:3098-3106, 1987), and a transfectant cell line expressing the same mutant kinase, showed increased sensitivity to a number of drugs that are known to be substrates for the multidrug transporter (P-glycoprotein). In the current study we have investigated the mechanism by which cAMP-dependent protein kinase controls drug resistance. We report here that the sensitivity of the kinase defective CHO cell lines to multiple drugs results from decreased RNA levels for the multidrug-resistance gene. Similar results were obtained with mouse Y1 adrenal cells. Wild-type Y1 cells had high levels of P-glycoprotein due to expression of both the mdr1b and mdr2 genes, whereas the cAMP-dependent protein kinase mutant Kin 8 cells had decreased RNA levels for these genes. A Kin 8 transfectant with restored cAMP-dependent protein kinase activity recovered mdr expression, indicating a cause and effect relationship between the protein kinase mutations and mdr expression. No changes in nuclear run-off assays could be detected, suggesting a non-transcriptional mechanism of regulation. Wild-type Y1 cells are more drug sensitive despite having higher levels of P-glycoprotein than the mutant cells. This paradoxical result may be explained by the higher rate of synthesis of steroids by the wild-type Y1 cells, which appear to be inhibitors of P-glycoprotein transport activity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1992

Rabbit knee immobilization: bone remodeling precedes cartilage degradation.

This study analyzed processes underlying osteoporosis and osteoarthrosis after short-term immobilization of the right hind limb of postadolescent (2.8 kg) and mature (4.0 kg) rabbits. After 3 weeks, the lateral posterior aspect of the lateral tibial plateau and the lateral femoral condyle of the immobilized limb exhibited prominent subchondral vascular eruptions. Femoral metaphyseal bone density decreased 27 and 18% in the immobilized limbs of postadolescent and mature rabbits, respectively. Calcein green fluorescence increased 1.9-fold (p less than 0.001) in the metaphyseal trabeculae of immobilized femurs. With immobilization, sulfate incorporation into femoral cartilage glycosaminoglycan increased, although total cartilage glycosaminoglycan and hydroxyproline levels were unchanged. Thymidine incorporation into DNA increased four- to fivefold in tibial and femoral cartilage of the immobilized limb. In this study, bone loss and remodeling preceded erosive cartilage degradation.

Animals↗
PubMed1992

Modulation of single-unit activity in the rat medial amygdala by neurotransmitters, estrogen priming, and synaptic inputs from the hypothalamus and midbrain.

The medial amygdala (m-AMG) appears to act as an integrative center for sensory, synaptic, and endocrine signals important in the regulation of reproductive function. Extracellular single-unit recordings from anesthetized, ovariectomized female rats were used to investigate neuropharmacological, hormonal, and synaptic modulation of neurons in the m-AMG. Electrical stimulation of the ventromedial hypothalamus (VMH) elicited excitatory or inhibitory orthodromic responses in 72% and antidromic responses in 7% of m-AMG neurons, whereas stimulation of the midbrain central gray (MCG) induced orthodromic responses in 43% of m-AMG neurons. Interestingly, most cells that were influenced by MCG stimulation were also orthodromically driven by the VMH, as 40% of all m-AMG cells responded orthodromically to both the VMH and MCG. Furthermore, the majority of these cells tended to be modulated by both areas in the same direction. Iontophoretic application of glutamate, GABA, ACh, and LHRH could modulate the spontaneous firing rate of m-AMG neurons. In particular, ACh had a predominantly excitatory action, which was more effective on m-AMG neurons that were orthodromically driven by the VMH and that were from estrogen-primed animals. In addition to increasing chemical responsiveness to ACh, estrogen priming of ovariectomized animals also increased the spontaneous firing rate of m-AMG neurons and decreased the number of silent cells. These modulatory actions on m-AMG neurons may be important in the medial amygdala's regulation of the behavioral and endocrine aspects of reproductive function in the female rat.

Amygdala↗
PubMed1992

Comparison of apical leakage in teeth obturated with a polyamide varnish or zinc oxide and eugenol cement using lateral condensation.

The sealing ability of copal varnish has been investigated when used as an adjunct in restorative procedures, retrofilling procedures, and dontic obturation procedures. Barrier, a polyamide-type polymer cavity varnish, has been compared with copal varnishes in restorative dentistry. This investigation compared the apical sealing properties of a zinc oxide and eugenol sealer (Roth) with a polyamide varnish (Barrier). Twenty-four teeth were instrumented and divided into two groups, one obturated with gutta-percha and Roth sealer and one with gutta-percha and Barrier, using submersion in methylene blue dye to demonstrate apical leakage. Roth sealer exhibited less dye penetration than Barrier when used as an endodontic sealant (p < 0.02).

Dental Cavity Lining↗
PubMed1992

Delayed root canal therapy: an analysis of treatment over time.

A retrospective study of 898 teeth receiving root canal therapy was performed to document the sequelae of delayed completion of root canal treatment. Teeth were categorized into a prompt treatment group and a delayed treatment group. Comparisons of prompt and delayed treatment groups were made with regard to preoperative pain, interappointment emergencies, postobturation pain, and final treatment. Findings from this study show that a palliative endodontic procedure is an extremely effective treatment. However, 56% of teeth with incomplete root canal therapy eventually were extracted compared with 2 to 3% for the root canal filling treatment groups. By emphasizing the potential loss of the tooth rather than the potential of interappointment emergencies, the clinician may be more effective in achieving compliance among patients receiving delayed treatment.

Acute Disease↗
PubMed1992

MIPSY: real-time morphometry to quantify the time course of rapid epithelial restitution.

The gastrointestinal mucosa has the ability to repair itself rapidly following superficial mucosal injury by rapid epithelial restitution. The mechanism consists of cell migration and does not involve mitosis. This study reports the mechanisms of rapid epithelial restitution in the rabbit colon in vivo and in the human colon in vitro, describes a new computerized real-time morphometry system to investigate the time course of restitution and presents a new method to calculate the migration speed of epithelia during the repair process. Superficial mucosal damage to the rabbit colon in vivo was produced by luminal exposure to 100 mM HCl for 5 min (80% of mucosal surface), a comparable injury in the human colon in vitro was obtained by luminal exposure to 10 mM HCl for 10 min (96% of mucosal surface). After detachment of the damaged tissue the intact epithelial cells in the vicinity of the necrosis extended pseudopodia and migrated over the denuded basal lamina. The morphological appearance of rapid epithelial restitution was the same in the rabbit and the human, only the time course was postponed in the human. The time course of rapid restitution was assessed by a newly developed computerized morphometry system (MIPSY). When tissues were examined after various time points following acid damage, 61% of the mucosa were damaged in the rabbit after 1 h, 10% after 2 hs and 20% after 5 hs. In the human colon 85% of the mucosal surface were damaged after 2 hs and 20% 5 hs after the end of acid exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

Chemical design of peripherally acting compounds.

1. Some guanidines, related in structure to mianserin and to 2-methyl-1,2,9,13b-tetrahydro-3H-dibenz[c,f]imadazo[1,5a] azepin-3-imine hydrobromide (WAL 801), have been synthesized and shown to be peripherally acting 5-HT2 antagonists. Structurally related compounds but not bearing a charged ionic group have been shown to have central activity. 2. Computer-aided molecular modelling has been used to establish a 5-HT2 pharmacophore. 3. The principle of exclusion from the CNS by incorporating a highly polar group to a biologically active molecule has been extended to the design and synthesis of a peripherally acting analgesic.

Computer Simulation↗
PubMed1992

Plasma volume expansion with colloids increases blood-tissue albumin transport.

Extravasation of plasma proteins is increased after volume expansion with whole blood or plasma. To investigate the mechanisms responsible for this phenomenon, we measured extravascular accumulation of exogenous 131I-labeled bovine serum albumin in several tissues and organs of anesthetized rats. Plasma volume was increased acutely by infusion of isoncotic albumin or polyvinylpyrrolidone, with or without subsequent infusion of a 1:10 dilution of the colloid to induce blood-to-tissue fluid movement. Controls were given only a slow sustaining infusion of saline. The amounts of fluid and plasma protein lost from the circulation were followed simultaneously by two methods: 1) material balance in the whole animal, and 2) changes in 131I-labeled albumin uptake (VA) and water content (VW) in the individual tissues. Plasma volume expansion of 80-90% increased plasma protein extravasation in the whole rat by an average of 2.7-fold over a 30-min period. Of the protein extravasated, 42% entered the abdominal cavity. The rest was distributed in the interstitial compartment of various tissues and organs. Tracer albumin accumulation (averaged over 30 min) was increased 38-82% in skin and paw, 40-59% in skeletal muscles, 131% in hearts, and 167-230% in different parts of the intestine. Increased convective transport does not appear to be a major factor. There was little or no relation of albumin transport increase to the magnitude or direction of net fluid transfer. Coupling of albumin transport to volume flow was not greater than previously reported for saline infusion or venous congestion. Convective redistribution (convective transport without net fluid transfer, "volume recirculation") is estimated to increase albumin transport no more than 10% under the conditions of our experiments. The greater part of the increase is thus dissipative, i.e., attributable to increased diffusion or increased vesicular exchange. Control of dissipative transport of albumin may play an important role in regulating plasma volume.

Animals↗
PubMed1992

Bromocriptine and Triac therapy for hyperthyroidism due to pituitary resistance to thyroid hormone.

Although a number of patients with generalized resistance to thyroid hormone have been treated with bromocriptine (Brc), only one previously reported patient with nontumoral TSH-mediated hyperthyroidism, presumably due to pituitary resistance to thyroid hormone (PRTH), has been successfully treated with bromocriptine (Brc). In addition, several studies suggested that the T3 analog 3,5,3'-triiodothyroacetic acid (Triac) may control hyperthyroidism in patients with PRTH. In the current study a patient with PRTH diagnosed at age 15 yr underwent separate therapeutic trials with Brc and Triac, during which time physical parameters, thyroid function tests, systolic time intervals (STI), and oxygen consumption (VO2) were measured. On Brc therapy (12.5 mg/day), heart rate decreased (108 to 72/min), TSH decreased (5.7 to 1.2 mU/L), T3 decreased (9.9 to 1.7 nmol/L), free T4 decreased (205 to 21 pmol/L), STI lengthened (left ventricular ejection time, 0.389 to 0.405 s), and VO2 did not change (164 to 162 mL/min). We found no significant clinical improvement with a maximal dose of Triac (2.1 mg/day), only minimal reduction in goiter size; mild decreases in T3 (9.9 to 6.7 nmol/L), free T4 (205 to 113 pmol/L), and TSH (5.7 to 5.4 mU/L); no change in STI (left ventricular ejection time, 0.389 to 0.401 sec); and an increase in O2 consumption (VO2, 164 to 209 mL/min). Thus, the results favor Brc as effective therapy for this patient with PRTH.

Adolescent↗
PubMed1992

The causal relationship between mutations in cAMP-dependent protein kinase and the loss of adrenocorticotropin-regulated adrenocortical functions.

The Y1 adrenocortical tumor cell mutants, Kin-7 and Kin-8, harbor point mutations in the regulatory subunit (RI) of the type 1 cAMP-dependent protein kinase (cAMPdPK) that render the enzyme resistant to activation by cAMP. These mutants also are resistant to many of the regulatory effects of ACTH and cAMP. In order to examine the causal relationships between the mutations in cAMPdPK and the resistance to ACTH and cAMP, the Kin mutants were transfected with expression vectors encoding wild type subunits of cAMPdPK in order to restore cAMP-responsive protein kinase activity. The transformants then were screened for the concomitant recovery of cellular responsiveness to ACTH and cAMP. In the mutant Kin-7, cAMP-responsive protein kinase activity was recovered after transfection with an expression vector encoding wild type mouse RI. Protein kinase activity in the mutant Kin-8 remained largely cAMP-resistant after transfection with the RI expression vector but could be rendered cAMP-responsive by transfection with an expression vector encoding the wild type catalytic subunit. The recovery of cAMP-responsive protein kinase activity was accompanied by the recovery of steroidogenic and morphological responses to ACTH and cAMP, suggesting that the cAMP-dependent signaling cascade plays an obligatory role in these actions of ACTH. The growth-regulatory effects of cAMP were not reversed with the recovery of cAMP-responsive protein kinase activity, suggesting that cAMP-resistant growth regulation results from second-site, adaptive mutations either in the original Kin mutant population or in the transformants. Studies on the conversion of 22(R)-hydroxycholesterol into steroid products in parent and mutant cells indicate that the Kin mutations reduce the steroidogenic capacity of the cell as well as inhibit the hormone- and cyclic nucleotide-dependent mobilization of substrate cholesterol.

Adenylyl Cyclases↗
PubMed1992

Optic neuropathy: a rare paraneoplastic syndrome.

A 63-year-old man developed gradually progressive bilateral loss of vision, cerebellar ataxia, and downbeat nystagmus. Visual acuity was 20/400 OD and 20/200 OS, with cecocentral scotomas OU. Fundus examination showed bilateral optic atrophy and a vitreous cellular reaction. MRI of the brain was normal. CSF protein was elevated, with increased IgG levels but no malignant cells. Biopsy of a pulmonary lymph node showed undifferentiated small cell carcinoma. Neoplastic cells were positive for neuron-specific enolase. Serum contained IgG, which reacted with neuronal and glial cytoplasm and processes. IgG reactivity with systemic tissues and the patient's tumor was not different from that observed with control sera. Paraneoplastic optic neuropathy should be considered in patients with unexplained visual loss and malignancy, and our observations suggest a possible immunologic basis for this condition.

Antineoplastic Agents↗
PubMed1992

Long-term and short-term electrophysiological effects of estrogen on the synaptic properties of hippocampal CA1 neurons.

The ovarian steroids exert both long-term and short-term actions on neurons involving different cellular mechanisms. We have investigated the long-term and short-term effects of estrogen on the electrophysiological properties of CA1 neurons utilizing intracellular recordings in hippocampal slices prepared from ovariectomized female rats. An in vivo estrogen-priming paradigm was used to examine long-term genomic actions of estrogen. Subcutaneous estrogen injections 2 d prior to recording had no effect on the intrinsic membrane properties of CA1 neurons, but increased synaptic excitability by prolonging the EPSP and inducing repetitive firing in response to Schaffer collateral stimulation. Short-term effects of estrogen that presumedly involve direct membrane interactions were tested by application of steroids directly to the slice. Superfusion of 17 beta-estradiol, but not 17 alpha-estradiol, caused a rapid and reversible increase in the amplitude of the Schaffer collateral-activated EPSP. This potentiation of the EPSP by 17 beta-estradiol still occurred in the presence of the NMDA antagonist 2-amino-5-phosphonovalerate, but was blocked by the non-NMDA antagonist 6-cyano-7-nitroquinoxaline-2,3-dione. Depolarizing responses to iontophoretic pulses of exogenous glutamate were also potentiated by 17 beta-estradiol, suggesting a post-synaptic site of action. In addition, 17 beta-estradiol potentiated the responses to alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid, kainate, and quisqualate, but not NMDA, further implicating non-NMDA receptors in the short-term action of estrogen. In contrast, 17 beta-estradiol had no effect on responses to exogenous GABA or on the Schaffer collateral-induced late IPSP.(ABSTRACT TRUNCATED AT 250 WORDS)

2-Amino-5-phosphonovalerate↗
PubMed1992

Self-care instructions: do patients understand educational materials?

As health care providers we are not in a position to teach reading. We do, however, have a legal and an ethical obligation to provide patients with self-care instructions they can understand. Because the methods presented for enhancing patient understanding of self-care instructions are relatively new, and because nurses are just beginning to be aware of the need for such interventions, it will be a while before the ideal situation exists. Ideally, each pamphlet or set of instructions would be coded with the reading grade level needed to understand it and each patient's reading level would be recorded in the chart. Under such "perfect" circumstances it would be easy for nurses to provide patients with instructions at the appropriate reading level. For now, any step that nurses take toward making self-care a reality for patients who read poorly is a step in the right direction. People with poor reading skills are less adept at formulating questions than good readers because they lack vocabulary and the ability to analyze written material. Rather than be regarded as stupid, many choose not to verbalize their lack of understanding. This phenomenon puts a large group of patients at risk for health complications related to inadequate understanding of self-care directions.

Adult↗
PubMed1991

A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure.

BACKGROUND: To define better the efficacy of vasodilator therapy in the treatment of chronic congestive heart failure, we compared the effects of hydralazine and isosorbide dinitrate with those of enalapril in 804 men receiving digoxin and diuretic therapy for heart failure. The patients were randomly assigned in a double-blind manner to receive 20 mg of enalapril daily or 300 mg of hydralazine plus 160 mg of isosorbide dinitrate daily. The latter regimen was identical to that used with a similar patient population in the effective-treatment arm of our previous Vasodilator-Heart Failure Trial. RESULTS: Mortality after two years was significantly lower in the enalapril arm (18 percent) than in the hydralazine-isosorbide dinitrate arm (25 percent) (P = 0.016; reduction in mortality, 28.0 percent), and overall mortality tended to be lower (P = 0.08). The lower mortality in the enalapril arm was attributable to a reduction in the incidence of sudden death, and this beneficial effect was more prominent in patients with less severe symptoms (New York Heart Association class I or II). In contrast, body oxygen consumption at peak exercise was increased only by hydralazine-isosorbide dinitrate treatment (P less than 0.05), and left ventricular ejection fraction, which increased with both regimens during the 2 years after randomization, increased more (P less than 0.05) during the first 13 weeks in the hydralazine-isosorbide dinitrate group. CONCLUSIONS: The similar two-year mortality in the hydralazine-isosorbide dinitrate arms in our previous Vasodilator-Heart Failure Trial (26 percent) and in the present trial (25 percent), as compared with that in the placebo arm in the previous trial, (34 percent) and the further survival benefit with enalapril in the present trial (18 percent) strengthen the conclusion that vasodilator therapy should be included in the standard treatment for heart failure. The different effects of the two regimens (enalapril and hydralazine-isosorbide dinitrate) on mortality and physiologic end points suggest that the profile of effects might be enhanced if the regimens were used in combination.

Adolescent↗