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Biomedical subjects

D Chan

Publications and source records attributed to D Chan.

At least 109 records · Page 6Linked to original sources
PubMed1997

In vitro expression analysis of collagen biosynthesis and assembly.

While the generalised pathway of collagen biosynthesis is well understood, the specific molecular interactions that drive chain recognition and assembly and the formation of tissue-specific extracellular supramolecular structures have not been elucidated. This review focuses on the use of in vitro collagen expression systems to explore some of these fundamental questions on the molecular basis of normal and mutant collagen assembly. Three in vitro expression/assembly systems are discussed. Firstly, a simple cell-free transcription/translation system to study the initial stages of collagen chain assembly. Secondly, a novel T7-driven high level expression system, using a recombinant vaccinia virus expressing T7 RNA polymerase, in transiently transfected cells which allows appropriate postranslational modification and collagen folding. Thirdly, the more complex questions of normal and mutant collagen extracellular matrix assembly are addressed by stable transfection and expression in cells which allow the formation of a 'tissue equivalent' matrix during long-term culture.

Animals↗
PubMed1997

The effects of sprue design on the roughness and porosity of titanium castings.

PURPOSE: This study measured the effects of the sprue number and position on the roughness and porosity of cast titanium crowns. MATERIAL AND METHODS: Twenty-four complete veneer crown wax patterns were fabricated on a stainless steel die with a 30-degree bevel finish line. Twelve wax patterns were sprued with one 8-gauge wax sprue and the remaining 12 were double sprued. All patterns were invested with a phosphate bonded investment. Castings were made with a titanium casting, according to the manufacturer's instructions, with commercially pure titanium (> 99.5%) ingots. The castings were carefully cleaned and the surface roughness was measured with a profilometer. The specimens were then embedded and sectioned. Internal porosities were quantified with photographs by computerized image analysis. Data were analyzed with an ANOVA and the Student's t test with a confidence level of 95%. RESULTS: The roughness value of the occlusal third of the crowns for the single sprue group (Ra = 3.0 +/- 0.9 microns) was significantly higher than other measurements (p < 0.05). There were statistically significant differences in values of porosity areas between the single sprue group (1.5 +/- 0.7 mm2) and the double sprue group (0.2 +/- 0.2 mm2) (p < 0.01). The double sprue design resulted in a relatively smoother casting surface and less internal porosity than the single sprue design. CONCLUSIONS: Improvements in the degree of roughness and porosity of titanium crown castings were the result of the double sprue design.

Analysis of Variance↗
PubMed1997

Video-based versus paper-and-pencil method of assessment in situational judgment tests: subgroup differences in test performance and face validity perceptions.

On the basis of a distinction between test content and method of testing, the present study examined several conceptually and practically important effects relating race, reading comprehension, method of assessment, face validity perceptions, and performance on a situational judgement test using a sample of 241 psychology undergraduates (113 Blacks and 128 Whites). Results showed that the Black-White differences in situational judgment test performance and face validity reactions to the test were substantially smaller in the video-based method of testing than in the paper-and-pencil method. The Race x Method interaction effect on test performance was attributable to differences in reading comprehension and face validity reactions associated with race and method of testing. Implications of the findings were discussed in the context of research on adverse impact and examinee test reactions.

Black or African American↗
PubMed1997

Reactions to cognitive ability tests: the relationships between race, test performance, face validity perceptions, and test-taking motivation.

The relationships among race, face validity perceptions, test-taking motivation, and test performance on a cognitive ability test were examined. Undergraduates completed 2 parallel cognitive ability tests and a test reactions measure. Results showed that test-taking motivation was related positively to subsequent performance on a parallel test even after the effects of race and performance on the first test were controlled. The effect of race on subsequent test performance was found to be mediated partially by motivation that provided evidence that some portion of the Black-White difference in test performance may be explained through differences in test-taking motivation. Results also indicated that Black-White differences in face validity perceptions of the test may be a function of Black-White differences in test performance. Face validity perceptions of the test affected subsequent performance on the parallel test but only indirectly through test-taking motivation.

Achievement↗
PubMed1997

Racial subgroup differences in predictive validity perceptions on personality and cognitive ability tests.

The relationships between examinees' racial subgroup membership and their perceptions of the predictive validity of a widely used personality test (NEO Five Factor Inventory; P. T. Costa & R. R. McCrae, 1992) and a widely used cognitive ability test (Wonderlic Personnel Test; E. F. Wonderlic, 1984) were examined. Results from 241 undergraduates showed that Black examinees perceived the cognitive ability test as less valid than White examinees, whereas no significant Black-White difference in predictive validity perceptions was observed on the personality test. Results also indicated a significant but small positive association between performance on the cognitive ability test and predictive validity perceptions of the cognitive ability test. Contrary to predictions, there was little evidence that test performance mediated the relationship between race and predictive validity perceptions on the cognitive ability test. Conversely, predictive validity perceptions did not appear to account for any substantial portion of the racial subgroup differences in test performance.

Adult↗
PubMed1997

alpha 1-Proteinase inhibitor in gingival crevicular fluid of humans with adult periodontitis: serpinolytic inhibition by doxycycline.

The serum protein, alpha 1-proteinase inhibitor (alpha 1-PI), defends the host against serine proteinases, e.g. PMN elastase. Using a rabbit anti-serum against human alpha 1-PI, this protein in GCF was quantified from a standard curve constructed from dot-blot analysis and characterized by Western blot. GCF was collected on filter paper strips from healthy (H), gingivitis (G) and adult periodontitis (AP) patients, then extracted with Tris/NaCl/CaCl2 buffer, pH 7.6. alpha 1-PI concentration increased with G and was highest in AP subjects. H sites only showed intact alpha 1-PI (52 kDa); no degradation fragments (48 kDa) were detected. In G and AP subjects, alpha 1-PI degradation fragments were seen in 17% and 71% of GCF samples, respectively. Both collagenase and alpha 1-PI-degrading activities in GCF increased with severity of inflammation (GCF flow). Moreover, the alpha 1-PI degrading (or serpinolytic) activity was characterized as a matrix metalloproteinase, probably collagenase, based on its in vitro response to a panel of different proteinase inhibitors including doxycycline. We propose: (1) that collagenase promotes periodontal breakdown not only by degrading collagen, but also by depleting alpha 1-PI regulation of elastase and other serine-proteinases, thereby favoring a broader attack on extracellular matrix (ECM) constituents, and (2) based on a recent longitudinal double-blind study using the techniques described above for alpha 1-PI analysis, that low-dose doxycycline administration to humans with adult periodontitis can inhibit this broad cascade of ECM degradation.

Adult↗
PubMed1997

The dopamine transporter gene and Parkinson's disease in a Chinese population.

We studied a variable number tandem repeat polymorphism within the dopamine transporter gene (DAT) for an association with Parkinson's disease in a Chinese population. Five alleles were detected, consisting of 6, 8, 9, 10, and 11 copies of the 40 base pair repeat sequence. The 10-copy allele was most common, accounting for 90% of alleles. There were no significant differences between the patients and the control subjects in the distribution frequencies of the alleles or genotypes. Therefore, this polymorphism is not associated with Parkinson's disease in Chinese populations.

Aged↗
PubMed1997

Molecular detection of minimal residual disease for patients with leukaemia and lymphoma.

Although a complete clinical remission can often be achieved with chemotherapy for patients with leukaemia and lymphoma, relapses still occur. Residual tumour cells probably have survived therapy and account for subsequent disease relapse. The sensitivity of conventioned ways of detecting residual tumour cells, such as morphological studies, immunophenotyping, and cytogenetics, is only about 1% to 5% and may be inadequate. Polymerase chain reaction technology has provided a simple and highly sensitive means for the detection of minimal residual disease. The technology has been successfully applied to study biopsy samples obtained from patients with leukaemia and lymphpma. Its clinical usefulness, however, requires further evaluation by prospective clinical studies.

Journal Article↗
PubMed1996

Multiexon deletions in the type I collagen COL1A2 gene in osteogenesis imperfecta type IB. Molecules containing the shortened alpha2(I) chains show differential incorporation into the bone and skin extracellular matrix.

Osteogenesis imperfecta (OI) type IB is a rare subset of the mildest form of OI, clinically characterized by moderate bone fragility, blue sclera, and dentinogenesis imperfecta. Cultured skin fibroblasts from two unrelated individuals (OI-197 and OI-165) with the typical features of OI type IB produced shortened alpha2(I) chains. Reverse transcription-polymerase chain reaction of the alpha2(I)-cDNA revealed deletions in the triple helical domain of 5 exons (exons 7-11) in OI-197, and 8 exons (exons 10-17) in OI-165. This exon skipping was caused by genomic deletions in one allele of COL1A2 with the breakpoints located in introns 6 and 11 in OI-197, and introns 9 and 17 in OI-165. The secretion and deposition of the mutant collagen into the matrix was measured in vitro in cultures of skin fibroblasts and bone osteoblasts, grown in the presence of ascorbic acid to induce collagen matrix formation and maturation, as well as in collagen extracts from skin and bone. The secretion of mutant collagen was impaired and long term cultures of fibroblasts showed that the mutant collagen was not incorporated into the mature collagenous matrix produced in vitro by skin fibroblasts from both patients. Likewise, the shortened alpha2(I) chain was not demonstrable in skin extracts. In contrast, bone extracts from OI-197 showed the presence of the mutant collagen. This incorporation of the abnormal collagen into the mature matrix was also demonstrated in long term cultures of the patient's osteoblasts. The deposition of the mutant collagen by bone osteoblasts but not by skin fibroblasts demonstrates a tissue specificity in the incorporation of mutant collagen into the matrix which may explain the primary involvement of bone and not skin in these patients.

Adolescent↗
PubMed1996

Site-directed mutagenesis of human type X collagen. Expression of alpha1(X) NC1, NC2, and helical mutations in vitro and in transfected cells.

Type X collagen is a short chain collagen expressed in the hypertrophic zone of calcifying cartilage during skeletal development and bone growth. The alpha1(X) homotrimer consists of three protein domains, a short triple helix (COL1) flanked by nonhelical amino-terminal (NC2) and carboxyl-terminal (NC1) domains. While mutations of the NC1 domain result in Schmid metaphyseal chondrodysplasia, which suggests a critical role for this protein domain, little biochemical detail is known about type X collagen synthesis, secretion, and the mechanisms of molecular assembly. To study these processes, a range of mutations were produced in human alpha1(X) cDNA and the biochemical consequences determined by in vitro expression, using T7-driven coupled transcription and translation, and by transient transfection of cells. Three NC1 mutants, which were designed to be analogous to Schmid mutations (1952delC, 1963del10, and Y598D), were unable to assemble into type X collagen homotrimers in vitro, but the mutant chains did not associate with, or interfere with, the efficiency of normal chain assembly in co-translations with a normal construct. Expression in transiently transfected cells confirmed that mutant type X collagen assembly was also compromised in vivo. The mutant chains were not secreted from the cells but did not accumulate intracellularly, suggesting that the unassociated mutant chains were rapidly degraded. In-frame deletions within the helix (amino acid residues 72-354) and the NC2 domain (amino acid residues 21-54) were also produced. In contrast to the NC1 mutations, these mutations did not prevent assembly. Mutant homotrimers and mutant-normal heterotrimers were formed in vitro, and the mutant homotrimers formed in transiently transfected cells had assembled into pepsin-stable triple helical molecules which were secreted.

Animals↗
PubMed1996

An alpha 1(II) Gly913 to Cys substitution prevents the matrix incorporation of type II collagen which is replaced with type I and III collagens in cartilage from a patient with hypochondrogenesis.

A heterozygous mutation in the COL2A1 gene was identified in a patient with hypochondrogenesis. The mutation was a single nucleotide transition of G3285T that resulted in an amino acid substitution of Cys for Gly913 in the alpha 1(II) chain of type II collagen. This amino acid change disrupted the obligatory Gly-X-Y triplet motif required for the normal formation of a stable collagen triple helix and prevented the deposition of type II collagen into the proposita's cartilage, which contained predominantly type I and III collagens and minor amounts of type XI collagen. Biosynthetic analysis of collagens produced and secreted by the patient's chondrocytes cultured in alginate beads was consistent with the in vivo matrix composition, demonstrating that the main products were type I and III collagens, along with type XI collagen. The synthesis of the cartilage-specific type XI collagen at similar levels to controls indicated that the isolated cartilage cells had re-differentiated to the chondrocyte phenotype. The chondrocytes also produced small amounts of type II collagen, but this was post-translationally overmodified and not secreted. These data further delineate the biochemical and phenotypic consequences of mutations in the COL2A1 gene and suggest that cartilage formation and bone development can take place in the absence of type II collagen.

Adult↗
PubMed1996

Paramedic vs private transportation of trauma patients. Effect on outcome.

BACKGROUND: Prehospital emergency medical services (EMS) play a major role in any trauma system. However, there is very little information regarding the role of prehospital emergency care in trauma. To investigate this issue, we compared the outcome of severely injured patients transported by paramedics (EMS group) with the outcome of those transported by friends, relatives, bystanders, or police (non-EMS group). DESIGN: We compared 4856 EMS patients with 926 non-EMS patients. General linear model analysis was performed to test the hypothesis that hospital mortality is the same in EMS and non-EMS cases, controlling for the following confounding factors, which are not affected by mode of transportation: age, gender, mechanism of injury, cause of injury, Injury Severity Score (ISS), and severe head injury. Crude, specific, and adjusted mortality rates and relative risks were also derived for the EMS and non-EMS groups. SETTING: Large, urban, academic level I trauma center. PATIENTS: All patients meeting the criteria for major trauma. RESULTS: The two groups were similar with regard to mechanism of injury and the need for surgery or intensive care unit admission. The crude mortality rate was 9.3% in the EMS group and 4.0% in the non-EMS group (relative risk, 2.32; P < .001). After adjustment for ISS, the relative risk was 1.60 (P = .002). Subgroup analysis showed that among patients with ISS greater than 15, those in the EMS group had a mortality rate twice that of those in the non-EMS group (28.8% vs 14.1%). After controlling for confounding factors, the adjusted mortality among patients with ISS greater than 15 was 28.2% for the EMS group and 17.9% for the non-EMS group (P < .001). CONCLUSIONS: Patients with severe trauma transported by private means in this setting have better survival than those transported via the EMS system. Large prospective studies are needed to identify the factors responsible for this difference.

Adult↗
PubMed1996

Evaluation of a new, integral, whole blood filter (RS2000) system for prestorage leucodepletion of SAG-M red cells.

Residual donor leucocytes are responsible for many adverse transfusion reactions. Prestorage leucodepletion may ameliorate these effects and enhance product quality. We studied a bottom and top (BAT) system incorporating an integral filter for whole blood leucodepletion. Our evaluation assessed leucodepletion efficiency as well as in vitro SAG-M red cell quality and storage characteristics. Sixty-six units of blood were collected; test units into the Optipac-pLuS system and controls into the standard triple pack configuration. Test units were held for 4-6 h at room temperature (rt) or 12-18 h at 4 degrees C. The mean leucocyte counts for the SAG-M red cells in the quality and storage trial were 0.6 x 10(6) (rt hold), 0.05 x 10(6) (4 degrees C hold) and 2500 x 10(6) (controls). We observed no significant differences between the groups for Na+, ATP, 2,3-DPG, glucose, lactate and pH during the 49 d storage. The control group, however, showed a greater increase in haemolysis and K+ with time. Autologous in vivo 24 h red cell recovery, after 42 d storage, was > 75%. Adjustment of processing parameters in subsequent studies gave leucodepleted SAG-M red cells with minimal cell loss (9.19%) plus acceptable haemoglobin content (46-76 g/U) and haematocrit (54-62%). This system achieved > 3.5 log leucodepletion with all but one unit containing < 1 x 10(6) leucocytes. The product quality is good and the system suitable for routine use in blood centres.

Blood Component Removal↗
PubMed1996

Technical basis for EPA's proposed regulation on the cleanup of sites contaminated with radioactivity.

The U.S. Environmental Protection Agency is proposing a regulation for the protection of the public from radioactive contamination at sites that are to be cleaned up and released for public use. The rule will apply to sites under the control of Federal agencies, and will impose limits on radiation doses to individuals living or working on a site following cleanup; it will thereby provide site owners and managers with uniform, consistent cleanup criteria for planning and carrying out remediation. This paper presents an overview of EPA's approach to assessing some of the beneficial and adverse effects associated with various possible values for the annual dose limit. In particular, it discusses the method developed to determine how the choice of cleanup criterion affects (1) the time-integrated potential numbers of non-fatal and fatal radiogenic cancers averted among future populations, (2) the occurrence of radiogenic cancers among remediation workers and the public caused by the cleanup process itself, and (3) the volumes of contaminated soil that may require remediation. The analytic methods described here were used to provide input data and assumptions for the Regulatory Impact Analysis (RIA) that supports the proposed regulation; the RIA also considered non-radiological benefits and costs (i.e., public health, economic, and ecological) of the standards.

Radiation Injuries↗
PubMed1996

Improved outcomes following the introduction of surfactant to an Australian neonatal unit.

OBJECTIVE: To study the impact of the introduction of artificial surfactant therapy for hyaline membrane disease (HMD) in an Australian neonatal intensive care unit. METHODOLOGY: Infants < 32 weeks gestation admitted between June 1991 and Dec 1993 who received treatment with artificial surfactant were compared with infants admitted during the preceding 30 months who would have been candidates for such treatment. RESULTS: For treated infants with gestations in the range 24-27 weeks, there was a significant reduction in neonatal death (adjusted odds ratio 0.28) and a significant increase in the incidence of chronic lung disease (CLD) (adjusted odds ratio 3.4). With gestations in the range 28-31 weeks, there was no significant change in neonatal death or CLD, but there was a significant reduction in incidence of pneumothorax (adjusted odds ratio 0.32). CONCLUSIONS: A reduced incidence of pneumothorax and neonatal death following the introduction of artificial surfactant therapy was readily demonstrable in the Australian setting.

Australia↗
PubMed1996

Disrupted growth plates and progressive deformities in osteogenesis imperfecta as a result of the substitution of glycine 585 by valine in the alpha 2 (I) chain of type I collagen.

The skeleton of a child with osteogenesis imperfecta type III, resulting from the substitution of glycine 586 by valine in the triple helical domain of the alpha 2 (I) chain of type I collagen, was severely porotic but contained lamellar bone and Haversian systems. From early childhood, structural failure of the bone resulted in the disruption of growth plates, progressive bone deformities, and severe growth retardation.

Adolescent↗