Biomedical subjects
Publications and source records attributed to Y Chan.
We describe here a case of Staphylococcus epidermidis prosthetic aortic valve endocarditis 9 y after valve replacement. Surprisingly, the microorganism was community-acquired, highly virulent and associated with splenic disease. The patient recovered following emergency valve replacement and prolonged antibiotic therapy. Splenectomy was not required.
Alpha-actinins belong to a family of actin-binding and crosslinking proteins and are expressed in many different cell types. Multiple isoforms of alpha-actinin are found in humans and are encoded by at least four distinct genes. Human skeletal muscle contains two sarcomeric isoforms, alpha-actinin-2 and -3. Previous studies have shown that the alpha-actinins function as anti-parallel homodimers but the question of heterodimer formation between two different isoforms expressed in the same cell type has not been explored. To address this issue, we expressed both alpha-actinin-2 and -3 in vitro and were able to detect their interaction by both blot overlay and co-immunoprecipitation methods. We were also able to demonstrate the presence of heterodimers in vivo in human skeletal muscle and in COS-1 cells transiently transfected with both isoforms. Our results clearly demonstrate the potential for alpha-actinin isoforms to form heterodimers which might have unique functional characteristics.
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BACKGROUND: The classical 'white coat response' to blood pressure measurement has been studied thoroughly. However, little is known about patients showing a reverse pattern, i.e. who have lower blood pressure readings at the clinic than outside healthcare facilities. AIM: To estimate the proportion of patients whose blood pressure levels as determined by self-measurements at home are higher than those taken at the clinic and to explore possible associations with demographic, clinical, and psychological variables. METHOD: Patients consecutively attending (n = 214) an academic family medicine department in Toronto, Canada, were eligible. Subjects aged below 16 years and those on psychotropic or blood pressure-lowering agents were excluded. The clinic-home blood pressure difference (CHBPD) was calculated for each participating subject by subtracting home blood pressure from clinic blood pressure. Those who had negative values were compared with the rest of the sample. RESULTS: A considerable proportion of patients had lower blood pressure at the clinic than at home (systolic, 34.6%; diastolic, 23.8%). These subjects did not differ from the rest of the sample with regard to age, sex, levels of education attained, immigration status, body mass index, experience of current symptoms, blood pressure levels, or psychological distress. However, in patients with a 'negative CHBPD', i.e. lower blood pressure at the clinic than at home, readings taken by an automatic, self-inflating device when still at the clinic were higher than in the rest of the sample. CONCLUSION: The results point to measurement bias being at least partly responsible for higher blood pressure readings outside the clinic. Automatic measurement devices used for self/home blood pressure measurement seem to cause an alerting reaction analogous to the well-described 'white coat response'.
Dystrophin, a component of the muscle membrane cytoskeleton, is the protein altered in Duchenne Muscular Dystrophy (DMD) and Becker Muscular Dystrophy (BMD). Dystrophin shares significant homology with other cytoskeletal proteins, such as alpha-actinin and spectrin. On the basis of its sequence similarity with alpha-actinin and spectrin, dystrophin has been proposed to function as dimer. However, the existence of both dimers and monomers have been observed by electron microscopy. To address this apparent discrepancy, we expressed dystrophin fragments composed of different domains in an in vitro translation system. The expressed fragments were tested for their ability to interact with each other and full-length dystrophin by both immunoprecipitation and blot overlay assays. These assays were successfully used to demonstrate the dimerization of alpha-actinin and spectrin, yet failed to detect any interaction between dystrophin fragments. Although these in vitro results do not prove that dystrophin is not a dimer in vivo, they do indicate that this interaction is not like that of the alpha-actinin and spectrin.
The complete nucleotide sequence of the genomic RNA of cymbidium mosaic potexvirus (CymMV) was determined to be 6227 nucleotides in length, excluding the poly (A) tail at the 3' terminus. Similar to other potexviruses, its genome organisation is comprised of five major open reading frames (ORFs 1 to 5), encoding a Mr 160 KDa putative RNA-dependent RNA polymerase (RdRp); a Mr 26KDa/13KDa/10KDa triple-gene-block (TGB) and a Mr 24 KDa coat protein. The CymMV encoded proteins shared a high degree of homology to their corresponding proteins of other members of the potexvirus group. The nucleotide sequence of the 5' noncoding region (NCR) of CymMV and all other potexviruses initiates with GAAAA. CymMV possesses the shortest 5' NCR among all potexviruses. Based on phylogenetic comparisons of RdRp and coat protein, CymMV shares a close relationship to PAMV, NMV, WClMV and SMYEaV. This is believed to be the first record of the complete nucleotide sequence of CymMV.
OBJECTIVE: Several reports have discussed a relationship between blood pressure (BP) and psychological well-being scales. Lower BP readings were associated with higher levels of psychological distress and fatigue. This study sought to replicate the association found by previous secondary analyses of epidemiological surveys. DESIGN: Cross-sectional study. SETTING: Academic Family Medicine Department in Toronto, Canada. SUBJECTS: 214 practice attenders. STUDY MEASURES: Extent of psychological abnormalities with the General Health Questionnaire (GHQ), self-reported fatigue, in-clinic and home BP measurements. RESULTS: No significant relationship between blood pressure levels and GHQ-score or fatigue could be demonstrated. This applies to clinic and home measurements for systolic and diastolic pressure. Neither adjustment for age or sex nor for several confounders through multiple linear regression produced significant associations in the postulated direction. No nonlinear relationship could be shown either. The study had a power of 95% to detect a correlation of r = 0.22 (alpha = 0.05, one-sided). CONCLUSION: The study specifically addressing the possible link between blood pressure and psychological dysfunction/fatigue, could not confirm the previously reported association. Problems related to type-I error in epidemiological research are discussed.
When several treatment methods are available for the same problem, many clinicians are faced with the task of deciding which treatment to use. Many clinicians may have conducted informal "mini-experiments" on their own to determine which treatment is best suited for the problem. These results are usually not documented or reported in a formal manner because many clinicians feel that they are "statistically challenged." Another reason may be because clinicians do not feel they have controlled enough test conditions to warrant analysis. In this update, a statistic is described that does not involve complicated statistical assumptions, making it a simple and easy-to-use statistical method. This update examines the use of two statistics and does not deal with other issues that could affect clinical research such as issues affecting credibility. For readers who want a more in-depth examination of this topic, references have been provided. The Kruskal-Wallis one-way analysis-of-variance-by-ranks test (or H test) is used to determine whether three or more independent groups are the same or different on some variable of interest when an ordinal level of data or an interval or ratio level of data is available. A hypothetical example will be presented to explain when and how to use this statistic, how to interpret results using the statistic, the advantages and disadvantages of the statistic, and what to look for in a written report. This hypothetical example will involve the use of ratio data to demonstrate how to choose between using the nonparametric H test and the more powerful parametric F test.
OBJECTIVE: To determine whether there is an association between the 'clinic-home blood pressure difference' (CHBPD) and psychological distress in a sample not selected without regard to blood pressure and hypertension status. DESIGN: A cross-sectional study. SETTING: An academic family medicine department in Toronto, Canada. PARTICIPANTS: Consecutive attenders (n = 214) of the primary care facility. Subjects aged less than 16 years and those being administered psychotropic or blood pressure-lowering agents were excluded. MAIN OUTCOME MEASURES: The CHBPD was calculated from clinic blood pressure readings and self-measurements by subjects at home; psychological distress was measured by the 30-item version of the General Health Questionnaire (GHQ). RESULTS: No significant association between the CHBPD and psychological distress could be shown for systolic and diastolic blood pressures. The same applied to GHQ subdomains and the CHBPD modelled on several independent variables by multiple linear regression analyses. CONCLUSION: The results from this study, using a large sample drawn from a community, support the view that the CHBPD is not related to anxiety, depression and other forms of psychological distress, but rather is a reaction specific to the clinic setting itself.
It is well known that glucagon-like peptide-1 (7-36 amide) (tGLP-1) is a potent insulinotropic hormone with powerful antidiabetogenic effects. In the present study we sought to determine the precise regions of the intracellular domains of the tGLP-1 receptor that are required for its efficient coupling to adenylyl cyclase because cAMP is the primary candidate second messenger coupling tGLP-1 to insulin secretion. Recently, we identified an amino acid within the third intracellular loop, K334, that was required for efficient coupling of tGLP-1 receptor to adenylyl cyclase. A similar mutagenesis-based strategy was employed here to examine the first and second intracellular loops and to further define sequences in the third loop required for the efficient coupling of the receptor to its second messengers. Receptor mutants were expressed in COS-7 cells and examined for tGLP-1 binding and cAMP stimulation. Three alanine substitution mutations, V327A, 1328A, and V331A, resulted in significantly lower tGLP-1-stimulated cAMP production without reductions in receptor expression. Analysis of the first and second intracellular loops revealed only one mutation contained within the first loop, R176A, where a significant reduction in cAMP activation was observed with normal receptor expression. These studies suggest that specific determinants of coupling for tGLP-1 receptor are primarily localized to the predicted junction of the fifth transmembrane helix and the third intracellular loop. We predict that V327, 1328, and V331 form part of a hydrophobic face that directly contacts the G protein.
OBJECTIVE: To compare whole body magnetic resonance imaging (MRI) using fast sequences with radioisotope bone scintigraphy (BS) for the detection of metastases in the entire skeleton. METHODS AND RESULTS: In forty-four patients suffering from carcinoma of lung, breast and prostate whole body MRI could generally be accomplished in about 39 minutes and it was shown to have a higher skeletal metastases detection compared with BS in the spine, pelvis, limb bones, sternum, scapula, and clavicle, but lower in the ribs and skull. CONCLUSIONS: We think for addressing the status of skeletal metastases only, bone scintigram is still preferred over whole body MRI. When bone scintigram is unavailable, whole body MRI is a practical and acceptable alternative especially when extra-osseous metastases are also of concern.
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Since their discovery, the function of intermediate filaments (IFs) has remained obscure. In skin, epidermal cells have extensive cytoskeletal architectures of IFs, composed of type I and type II keratin heterodimers. Clues to possible functions of these proteins have come from recent studies showing that several autosomal-dominant, blistering skin disorders are caused by defects in genes that encode epidermal keratins. These diseases all exhibit cell degeneration and keratin network perturbations in cells that express the particular mutant keratin gene. However, it is not clear from these studies whether cytolysis arises from the presence of large insoluble keratin aggregates that compromise cellular physiology or from the absence of an extensive keratin filament network, which jeopardizes mechanical integrity. We report here the analysis of an extremely rare case of severe recessive epidermolysis bullosa simplex (EBS), where the patient lacks a discernible keratin filament network in basal epidermal cells. Genetic analyses revealed a homozygous point mutation that yielded a premature termination codon in the major basal type I keratin gene and caused complete ablation of K14. The consanguineous parents were normal, each harboring one copy of the null K14 mutation. Analysis of cultured keratinocytes enabled us to document that the loss of K14 is not compensated for by the up-regulation of any other type I keratin. When taken together with the in vivo studies showing the presence of cell fragility generated from the lack of an extensive basal keratin network, these findings provide the first clear demonstration of loss of function associated with the absence of an IF protein in vivo.
The purpose of this study was to use microbiological tests for diagnosis of periodontal diseases in Taiwan. Anaerobic culture, direct microscopy, indirect immunofluorescence (IF), and biochemical tests were used to examine 336 samples for the specific microorganisms in subgingival plaque. The results indicated that gram-negative species and motile bacteria were less frequently detected, and in lower proportion, in samples from healthy sites. The bacteria found frequently in healthy group were the coccal forms. However, Bacteroides forsythus detected by IF showed a close association with periodontal inflammation. Porphyromonas gingivalis was found with about 53% frequency in the periodontitis group; in more than half the samples the proportion was above 5%. Actinobacillus actinomycetemcomitans was recovered with 48% frequency of periodontitis group. Other cultivable species including Campylobacter rectus, Capnocytophaga species, Centipeda periodontii, Eikenella corrodens, Fusobacterium nucleatum, Prevotella intermedia, Selenomonas species, and the Spirochetes were detected in a significantly higher proportion in periodontitis group. The results strongly support the use of microbiological tests as adjuncts to diagnosis, and for assessment of the importance of microbiota in periodontal disease.
We have developed a data base of lymphoid proteins detectable by two-dimensional polyacrylamide gel electrophoresis. The data base contains two-dimensional patterns and derived information pertaining to polypeptide constituents of unstimulated and stimulated mature T cells and immature thymocytes, single-cell-derived T- and B-cell clones, leukemia cells, and lymphoid cell lines. Using this data base, we have compared the protein constituents of mature T cells and immature thymocytes before and after mitotic stimulation. A subset of polypeptides that are induced in mature T cells following mitotic stimulation were found to be constitutively expressed in immature thymocytes. Other polypeptides exhibited differences in their expression between mature and immature thymocytes in a manner unrelated to proliferation. The identity of several constitutively expressed or mitotically induced proteins in lymphoid cells was established by microsequencing. These initial findings point to significant differences in the molecular pathways leading to proliferation between mature and immature T cells. The construction of this database should facilitate further studies of lymphoid differentiation and function.
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