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Biomedical subjects

C Wong

Publications and source records attributed to C Wong.

At least 199 records · Page 11Linked to original sources
PubMed1995

Lissencephaly gene (LIS1) expression in the CNS suggests a role in neuronal migration.

Miller-Dieker lissencephaly syndrome (MDS) is a human developmental brain malformation caused by neuronal migration defects resulting in abnormal layering of the cerebral cortex. LIS1, the gene defective in MDS, encodes a subunit of brain platelet-activating factor (PAF) acetylhydrolase which inactivates PAF, a neuroregulatory molecule. We have isolated murine cDNAs homologous to human LIS1 and mapped these to three different chromosomal loci (Lis1, Lis3, Lis4). The predicted sequences of murine Lis1 protein and its human homolog LIS1 are virtually identical. In the developing mouse and human, Lis1 and LIS1 genes were strongly expressed in the cortical plate. In the adult mouse Lis1 transcripts were abundant in cortex and hippocampus. The direct correlation between cortical defects in MDS patients and Lis1 expression in the murine cortex suggest that the mouse is a model system suitable to study the mechanistic basis of this intriguing genetic disease.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed1995

Total hip replacement: the case for noncemented femoral fixation because of age.

Both noncemented fixation and improved cemented fixation of total hip replacements emerged to counteract the clinical and radiographic failures of early cemented procedures. A randomized clinical trial comparing a second-generation cemented with a second-generation noncemented total hip replacement demonstrated that in the medium term both implants allow excellent, disease-specific, global and functional capacity outcome measures. No significant differences existed between the cemented and noncemented implants in terms of these parameters or revision rate. Cost-to-utility analyses of both types of replacements revealed that total hip replacement is one of the most cost-effective medical interventions. Noncemented total hip replacements seem as efficacious as cemented devices in patients younger than 70 years.

Adolescent↗
PubMed1994

Characterization and structural analysis of a functional human serum transferrin variant and implications for receptor recognition.

The nucleotide and amino acid substitutions leading to the only known functional variant of human serum transferrin have been characterized by sequencing of a peptide produced by cyanogen bromide digestion and genomic PCR coupled with cycle sequencing, respectively. There is an amino acid substitution at position 394 (Gly-->Arg) resulting from a mutational transition, G-->A, in the first nucleotide of the codon GGG. The Zn(2+)-, Al(3+)-, and Cu(2+)-binding properties of the variant, ascertained by UV difference spectra and, in the case of copper, protein fluorescence quenching, confirm that these metals binds to only one of the two sites. Solution X-ray scattering measurements indicate that the lobe (the C-lobe) containing the mutation remains "open" in the iron-bound state, and modeling studies suggest that this is a consequence of the formation of a salt bridge between Arg394 in the variant protein and Asp392, one of the iron-binding ligands in the C-lobe. This rationalizes for the first time the observed reduction in receptor affinity of the diferric variant protein for PHA-stimulated lymphocytes [Young, S.P., et al. (1984) Br. J. Haematol. 56, 581-587] and here repeated with K562 cells. These data lend support to the hypothesis that the closed conformation for both lobes contributes to receptor recognition.

Aluminum↗
PubMed1994

Does running cause gastrointestinal symptoms? A survey of 93 randomly selected runners compared with controls.

AIM: To investigate the belief that running causes diarrhoea and gastroesophageal reflux. METHODS: Diet and gastrointestinal symptom questionnaires were completed by 93 randomly selected runners and 95 age, sex matched sedentary controls. RESULTS: The runners ate more fibre and had more frequent bowel movements which were more often loose or urgent. They had less constipation but there was no difference in the use of laxatives or the prevalence of the irritable bowel syndrome. Although most runners tried to empty their bowels before running, the urgent need to have a bowel movement was still the most common reason for a runner to stop during a run. Heartburn, vomiting and bloating were more common when not training while retching, stitches and fecal incontinence were more common when running. Few runners ate before running and upper gastrointestinal symptoms while running were rare. CONCLUSIONS: Lower gastrointestinal symptoms may be caused by running or the running lifestyle. Upper gastrointestinal symptoms are not due to running alone.

Adult↗
PubMed1994

RNA polymerase binding using a strongly acidic hydrophobic-repeat region of sigma 54.

sigma 54 is a rare bacterial protein that substitutes for sigma 70 in the case of Escherichia coli genes transcribed by certain activators with enhancer protein-like properties. It contains a strongly acidic region of previously unknown function. Gel mobility-shift assays using sigma 54 deletion mutants show that this region is essential for sigma 54 to bind the core RNA polymerase and recruit it to the promoter. Multiple-point mutational analysis shows that the acidic amino acids and overlapping periodic hydrophobic amino acids are necessary for this binding. Related sequences are not found within the core binding determinant of sigma 70, which binds the same core RNA polymerase. This comparison suggests that the core RNA polymerase interacts differently with the two sigma factors, likely contributing to the critical differences in transcription mechanism in the two cases.

Amino Acid Sequence↗
PubMed1994

The domain structure of sigma 54 as determined by analysis of a set of deletion mutants.

Escherichia coli sigma 54 was analyzed by making a series of 16 internal deletions within its gene and analyzing the properties of the mutant proteins. All of the mutant proteins except one were strongly defective in a growth test that relied on sigma 54 function. Additional assays were applied to determine the causes of these defects. The assays monitored the following properties: the level of protein expression; ability to bind to the -24 promoter element of the glnAP2 promoter in vivo; the ability to bind to the -12 promoter element in vivo; ability to melt the promoter start site in vivo; ability to bind the Rhizobium meliloti nifH promoter in vitro; and the ability to form a sigma 54-core RNA polymerase complex (E sigma 54 holoenzyme) in vitro. The analysis shows a modular structure in that certain regions of the protein predominate in contributing to each of these properties. A large carboxyl region of the protein is essential for promoter binding. A smaller amino-terminal segment is essential for DNA melting. An element essential for the forming the E sigma 54 holoenzyme lies between these two regions. None of these domains resemble those of sigma 70 and this difference is discussed in view of the different transcription mechanisms directed by the two proteins.

Bacterial Proteins↗
PubMed1994

High-molecular-weight polypeptide substrates for phospholysine phosphatases.

The detection and characterization of the phosphatases responsible for the dephosphorylation of N-phosphoryl groups, such as phospholysine, in proteins has been frustrated in large measure by a lack of suitable substrates for the assay of these enzymes. Herein we describe the preparation of phospholysine-containing amino acid homo- and heteropolymers by chemical means, and their use in a simple, nonradioactive assay for phospholysine phosphatase activity.

Acid Phosphatase↗
PubMed1994

Transbilayer diffusion of divalent cations into liposomes mediated by lipidic particles of phosphatidate.

Liposomes formed from egg-yolk phosphatidylcholine:egg-yolk phosphatidate (molar ratio 2:1) containing pBR322 DNA and DNase I were induced to form, with divalent cations, bilayer/nonbilayer phase transitions of phosphatidate which allowed cation diffusion into liposomes; then cation diffusion was measured by the activation of the hydrolysis of DNase I on DNA. The formation of phosphatidate transitions on liposomes was demonstrated by freeze-fracture and 31P NMR, and a direct correlation between the formation of phosphatidate transitions and the transbilayer diffusion of cations was found: only Ca2+ and Mn2+, which induce phase transitions, were able to penetrate liposomes and triggered the DNase I activity; in addition, Ca2+ at higher concentrations (10 mM) caused fusion of liposomes, whereas Mn2+ did not, suggesting that transitions induced by Mn2+ participated only in the diffusion of this ion; furthermore, Mg2+ neither formed phase transitions nor triggered the enzymatic activity. The liposomes studied represent more dynamic structures that can form phosphatidate structures involved in both (1) the interchange of divalent cations with the surroundings, thereby modulating encapsulated enzymes, and (2) the fusion of lipid vesicles probably implicated in the enrichment of liposomal content in the early Precambian Earth.

Cations↗
PubMed1994

Pulmonary penicillosis marneffei: report of the first imported case in Canada.

A 57-year-old female, born in Laos and who had lived in Thailand prior to immigrating to Canada in 1989, was seen by her physician with a chief complaint of cough and dyspnea. Her chest X-ray showed bilateral pulmonary air fluid levels. A fungus, with a diffusible red pigment, tentatively identified as Penicillium marneffei, was isolated from the patient's bronchial washings and sputum specimens. At 37 degrees C, the fungus converted to a yeast form when cultured on brain heart infusion agar. Microscopic examination of this culture revealed yeast cells that reproduced by fission. The identity of the patient's isolate was confirmed as P. marneffei with an exoantigen test. The patient's serum demonstrated specific antibodies to P. marneffei antigen. Treatment with amphotericin B and ketoconazole resulted in clinical improvement, clearing of chest X-rays and conversion to sero-negativity. Our case is the first recorded diagnosis of imported penicillosis marneffei in Canada. The minimal inhibitory concentrations recorded for the patient's isolate to fluconazole, 5-fluorocytosine, itraconazole and miconazole were 12.5, 0.39, < 0.195 and < 0.195 micrograms/ml, respectively.

Amphotericin B↗
PubMed1994

Costs of elective total hip arthroplasty during the first year. Cemented versus noncemented.

The cost-effectiveness of the Mallory Head (Biomet, Warsaw, IN) cemented versus noncemented total hip arthroplasty was determined as part of a randomized trial. Costs were assessed during the first postoperative year. In-hospital resource use was determined using a chart review of 60 randomly selected patients. Costs were determined using a fully allocated costing model. Outpatient resource use was determined using patient diaries, and appropriate costs were allocated for outpatient visits, admissions to hospital, and patient-borne costs. There was no difference in costs between the cemented and noncemented prostheses. The average cost of the initial hospitalization was $9,990 (1988 Canadian dollars), and outpatient costs during the first year were $1,137 (total cost during the first year was $11,127). The cost per quality adjusted life year was $27,139 during the first year and $8,031 during the first 3 years.

Ambulatory Care↗
PubMed1994

Expression of the Kallmann syndrome gene in human fetal brain and in the manipulated chick embryo.

Kallmann syndrome is an inherited disorder characterized by an abnormality in olfactory system development. The gene for the X-linked form of this disorder (KAL) maps to Xp22.3 and encodes a protein sharing homologies with molecules involved in neuronal migration and axonal pathfinding. Here we report the expression pattern of the KAL gene in various parts of the human fetal brain. We found KAL transcripts in granule cells of the olfactory bulb and the cerebellum, in the dorsomedial thalamus and in the developing cerebral cortex. To determine whether or not signals from the olfactory nerve are required for KAL expression in the olfactory bulb, we analyzed chick embryos in which the olfactory placode was surgically removed. Those embryos lacking an olfactory nerve had a histologically abnormal bulb which nevertheless expressed the KAL gene at high levels. These findings indicate that, while the development of the proper cytoarchitecture of the olfactory bulb requires the innervation by olfactory axons, the expression of KAL is independent of such developmental processes.

Abortion, Induced↗
PubMed1994

The 1-month outcome of patients with a low probability Technegas ventilation/perfusion lung scan.

The objective was to study the 1-month outcome of patients who had a low probability ventilation/perfusion lung scan using Technegas radioaerosol as the inhalational agent and who did not receive anticoagulation. One hundred consecutive patients with suspected pulmonary embolism were studied retrospectively. Their Technegas lung scans were classified by two blinded and independent nuclear medicine physicians and the medical records of all patients with a low probability scan were reviewed. One hundred inpatients (42 males and 58 females) with a mean age of 63 years were studied. The three most common clinical presentations leading to lung scintigraphy were unexplained dyspnoea (30 cases), unexplained dyspnoea with pleuritic chest pain (26 cases) and pleuritic chest pain only (15 cases). Nine patients had been judged by their managing medical team to have a high clinical probability of true pulmonary embolism, 32 had an intermediate probability clinical presentation and 59 a low clinical probability of pulmonary embolism. None of the 100 patients experienced further episodes of suspected or proven pulmonary embolism during the follow-up period. Six patients died. In none of them was pulmonary embolism either the cause of or a major contributing factor to death. The finding of a low probability scan using Technegas as the ventilation scintigram agent of choice describes a group of patients who, even in the absence of therapeutic anticoagulation, have a favourable 1-month outcome free of either true or suspected clinical pulmonary embolism. Invasive, pulmonary angiography-based diagnostic strategies may not be needed in this group of patients.

Female↗
PubMed1994

Safety and efficacy of recombinant human erythropoietin in correcting the anemia of patients with chronic renal allograft dysfunction.

Recombinant human erythropoietin (rHuEPO) is effective in correcting anemia in hemodialysis, peritoneal dialysis, and predialysis patients. Limited studies in patients with failing renal allografts suggest a similar efficacy but provide little information concerning benefits, dose requirements, or adverse events. This study examined these considerations in a group of 40 patients (18 men; 22 women) aged 40.3 +/- 13.8 yr with stable, chronic renal allograft failure. All patients had a hemoglobin < 95 g/L and a serum creatinine > 250 mumol/L at baseline. Patients received rHuEPO (50 U/kg sc) three times weekly for 24 wk along with iron po if serum ferritin was < 100 micrograms/L. Mean hemoglobin rose from 78.9 +/- 10.4 to 102.6 +/- 18.4 g/L after 24 wk. Mean rHuEPO dose at 24 wk was 129.8 +/- 81.9 U/kg per week. With oral iron supplementation only, serum ferritin fell throughout the 24 wk, whereas serum iron, transferrin saturation, and total iron-binding capacity remained stable. Quality of life was assessed by use of the general Sickness Impact Profile and the disease-specific Transplant Disease Questionnaire measures at baseline and every 8 wk during rHuEPO therapy. Significant improvement was noted in global Sickness Impact Profile scores and in four of five dimensions of the Transplant Disease Questionnaire. Serious adverse events were infrequent. No change in mean systolic or diastolic blood pressure was noted, although there was a significantly increased need for antihypertensive drugs in 18 patients (P = 0.0002). A significant inverse correlation was noted between baseline renal function and maintenance rHuEPO dose (r = -0.45; P < 0.05). Twelve patients returned to dialysis during the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1994

A double-blind study of 250 cases comparing cemented with cementless total hip arthroplasty. Cost-effectiveness and its impact on health-related quality of life.

The success of a total hip arthroplasty (THA) is dependent on many more parameters than simply the prosthesis used. This study has demonstrated that a randomized controlled clinical trial of 250 patients comparing two types of hip prostheses (cemented versus cementless) with virtually complete follow-up examination is feasible. It also demonstrates that patients are willing to answer extensive quality-of-life questionnaires that allow complete assessment of the impact of hip arthroplasty on the patient's overall health-related quality of life. This study has also demonstrated that THA is an extremely effective intervention when one assesses its ability to impact on patients health-related quality of life with no difference between cement versus cementless at two years' follow-up examination.

Activities of Daily Living↗