Harm reduction in the health care system: the legality of prescribing and dispensing syringes to drug users.
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Blood-Borne Pathogens↗
Biomedical subjects
M Ng
Publications and source records attributed to M Ng.
Abdominal pain after endoscopic intervention.
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Aged↗
Deficiency of T2K leads to apoptotic liver degeneration and impaired NF-kappaB-dependent gene transcription.
Induction of NF-kappaB-dependent transcription requires phosphorylation and subsequent degradation of I-kappaB, an inhibitor of NF-kappaB, followed by nuclear translocation and DNA binding of NF-kappaB. Tumor necrosis factor receptor-associated factor 2 (TRAF2) plays a role in NF-kappaB activation in response to cytokines such as tumor necrosis factor alpha (TNFalpha). In this study, we purified and characterized a novel kinase (T2K, also known as TBK1 or NAK), which associates with TRAF2 and exhibits kinase activity towards I-kappaBalpha in vitro. The physiological function of T2K was investigated using T2K-deficient mice. Heterozygotes appear normal, but t2k(-/-) animals die at approximately E14.5 of massive liver degeneration and apoptosis. Never theless, hematopoietic progenitors from T2K-deficient fetal liver support normal lymphocyte development. Furthermore, t2k(-/-) embryonic fibroblasts and thymocytes do not display increased sensitivity to TNFalpha-induced apoptosis. In response to either TNFalpha or IL-1 induction, t2k(-/-) embryonic fibroblasts exhibit normal degradation of I-kappaB and kappaB-binding activity. However, NF-kappaB-directed transcription is dramatically reduced. These results demonstrate that, like I-kappaB kinase beta and the RelA subunit of NF-kappaB, T2K is critical in protecting embryonic liver from apoptosis. However, T2K has a unique role in the activation of NF-kappaB-directed transcription, apparently independent of I-kappaB degradation and NF-kappaB DNA binding.
Amino Acid Sequence↗
Ultrastructure of the Endolimax nana cyst.
This is the first report on the ultrastructure of the Endolimax nana cyst. These cysts are mostly ovoid in shape and have a distinct cyst wall measuring 80 nm. The nuclear membrane is without pores or associated chromatin deposits. The cytoplasm does not have mitochondria or a Golgi apparatus but shows elongated tubular structures made up of a double row of ribosome-like particles. The nature and function of this structure is not known, but it appears to be characteristic of this species and has not been reported from any other intestinal ameba.
Amebiasis↗
Scanning electron microscopy of Chilomastix mesnili (Wenyon 1910) Alexieieff, 1912.
Scanning electron microscopy of Chilomastix mesnili shows that the cysts are lemon-shaped with one end broadly rounded and the other conical. The trophozoite has five flagella coming out of the anterior end. Four of these are free and the fifth is attached to the body by an undulating membrane. The undulating membrane extends along the whole length of the body of the parasite with the exception of the tail. The tail is an elongated structure almost equal in length to the main body of the parasite.
Animals↗
Age-associated changes in decorin in rat mandibular condylar cartilage.
The small proteoglycan decorin strongly binds the fibrils of collagen types I and II; this interaction is thought to play a part in the maintenance of tissue integrity and biomechanical properties. In limb articular cartilage, there is evidence that decorin synthesis increases with age and that it is elevated in response to increased loading or in osteoarthritic cartilage. The aim here was to characterize the presence and relative amount of decorin in the condylar cartilage of the temporomandibular joint (TMJ) with maturation by Western blotting, and to assess its tissue localization by immunohistochemistry. Comparative data were obtained from tibial articular cartilage, which has been extensively studied. Cartilage from the mandibular condyle and tibial plateau was harvested from 24-day-old (growing) and 161-day-old (young adult) female Sprague-Dawley rats. In growing animals, decorin appeared slightly more abundant in the mandibular condylar cartilage than in articular cartilage, whereas in young adult animals the decorin content in the TMJ cartilage was noticeably less than in limb articular cartilage. Although there was an increase in decorin abundance with age at the TMJ, the increase in decorin with age in limb articular cartilage was considerably more pronounced. These data indicate that, although decorin is present in mandibular condylar cartilage, its abundance in adults is less than in limb articular cartilage; thus, maturation-associated changes may be dissimilar in magnitude from those documented for limb articular cartilage.
Aging↗
Requirement for Casper (c-FLIP) in regulation of death receptor-induced apoptosis and embryonic development.
Casper (c-FLIP) associates with FADD and caspase-8 in signaling complexes downstream of death receptors like Fas. We generated Casper-deficient mice and cells and noted a duality in the physiological functions of this molecule. casper-/- embryos do not survive past day 10.5 of embryogenesis and exhibit impaired heart development. This phenotype is reminiscent of that reported for FADD-/- and caspase-8-/- embryos. However, unlike FADD-/- and caspase-8-/- cells, casper-/- embryonic fibroblasts are highly sensitive to FasL- or TNF-induced apoptosis and show rapid induction of caspase activities. NF-kappaB and JNK/SAPK activation is intact in TNF-stimulated casper-/- cells. These results suggest that Casper has two distinct roles: to cooperate with FADD and caspase-8 during embryonic development and to mediate cytoprotection against death factor-induced apoptosis.
Animals↗
Microsatellite alterations in squamous cell carcinoma of the head and neck - clustering of loss of heterozygosity in a distinct subset.
Loss of heterozygosity (LOH) and microsatellite instability (MSI) have been recognized as important events in the carcinogenesis of many cancers, including squamous cell carcinoma of head and neck (SCCHN). However, microsatellite alterations have not been documented in SCCHN from Chinese patients. We investigated the frequency and clinical significance of LOH and MSI in 30 SCCHN from Hong Kong Chinese using polymerase chain reaction on 17 microsatellite markers on chromosomes 3p, 4q, 7q, 9p, 17p and 18q. LOH was present in nine tumours (30%) and MSI in four (13%). The incidence of LOH (7/13; 53.8%) in hypopharyngeal-laryngeal cancers was significantly higher than that (2/17; 11.8%) in the oral cancers (P=0.020). LOH was more often detected at the loci on chromosomes 7 and 9. Patients with tumours having LOH had slightly poorer outcome compared with those without, although the differences did not reach statistical significance. Our data show that the incidence of microsatellite alterations in SCCHN from Hong Kong Chinese is low. However, LOH may be one of the genetic mechanisms in the carcinogenesis of a subset of SCCHN (hypopharyngeal-laryngeal cancers).
Adolescent↗
Three ways to learn the ABCs.
The ABC model of flower development represents a milestone in explaining how the fate of emerging floral organ primordia is specified. This model states that organ identity is specified by different combinations of the activities of the A, B and C class homeotic genes. In spite of the remarkable simplicity of this model, the complex regulatory interactions that establish the initial pattern of A, B and C gene activity have yet to be fully explained. It has been shown that the LEAFY gene functions early to promote flower meristem identity, and that it is subsequently required for the normal expression of the ABC genes. Recently, LEAFY has been identified as an immediate upstream regulator of the floral homeotic genes, thus opening up an avenue to examine the transcriptional interactions that underlie floral patterning.
AGAMOUS Protein, Arabidopsis↗
Postnasal maturation of the human endolymphatic sac.
OBJECTIVE/HYPOTHESIS: The objective of this study was to trace the postnatal development of the human endolymphatic sac. The endolymphatic sac starts as a pouch-like structure during the fetal period in the human but later develops into a complex network of tubules in its mature form. STUDY DESIGN: Observational study. METHODS: Light microscopic examination of the morphology of the endolymphatic sac in a population of temporal bones. RESULTS: Examination of 28 temporal bones from 19 infants and children reveals that endolymphatic sac morphological maturation is usually completed in the first year of life, although it may occur as late as 4 years of age. There was good correlation of maturation levels between sides when pairs of temporal bones were evaluated. Immature pouch-like endolymphatic sacs may appear as late as 4 years of age. CONCLUSIONS: Endolymphatic sac maturation to its adult tubular form is usually completed by the first year. This finding contrasts with other studies examining the growth of the endolymphatic sac to adult size after birth. Histological evidence suggests that the endolymphatic sac, although not morphologically mature by appearance, may still be participating at some level of functioning.
Child, Preschool↗
Expression of P-glycoprotein in hepatocellular carcinoma. A determinant of chemotherapy response.
To characterize the P-glycoprotein (Pgp) expression in human hepatocellular carcinoma (HCC), we studied 101 cases of HCC treated with surgical resection without prior treatment. Pgp expression was detected immunohistochemically using 2 monoclonal antibodies (C494, C219) and correlated with pathologic features, survival, and p53 expression. Chemotherapy response was analyzed in a separate group of patients with inoperable HCC treated with systemic chemotherapy. Positive immunostaining was seen in 92% and 80% of the tumors with C494 and C219, respectively; bile canalicular type staining was seen in all positive tumors. Pgp expression was less extensive in the tumors than in the corresponding nontumorous liver tissue. Tumor Pgp expression with either antibody had no association with cellular differentiation, aggressive pathologic features, survival, or p53 overexpression. In patients with inoperable HCC, the chemotherapy response was significantly inversely related to Pgp expression with C494 and C219. Pgp was expressed in human HCC but was patchy and less extensive than in the nontumorous tissue. Response to systemic chemotherapy was inversely related to the level of Pgp expression in patients with inoperable tumors. Pgp expression in tumors not treated with chemotherapy was not associated with a more aggressive tumor phenotype or p53 overexpression and did not influence survival.
ATP Binding Cassette Transporter, Subfamily B, Mem↗
Self-reported physician practices for children with asthma: are national guidelines followed?
OBJECTIVE: To determine self-reported adherence to national asthma guidelines for children by primary care physicians in managed care; and, to analyze sources of variation in these practices by physician specialty and managed care practice type. DESIGN: A survey of 671 primary care physicians (pediatricians and family physicians) practicing in 3 geographically diverse managed care organizations (MCO). Domains of interest included asthma diagnosis, pharmacotherapy, patient education and follow-up, and indications for specialty referral. Item formats included self-reports of usual practice and responses to case vignettes. RESULTS: A total of 429 (64%) physicians returned surveys, 22 of whom did not meet criteria for inclusion in the analysis. Most respondents had both heard of (91%) and read (72%) the National Asthma Education and Prevention Program (NAEPP) guidelines. For diagnosis, 75% reported routine use of office peak flow measurement, but only 21% used spirometry routinely. Family physicians were more likely than pediatricians to use spirometry in diagnosis (odds ratio [OR] = 5.9), and less likely to recommend daily peak flow measurement (OR =.3). The median reported frequency of providing written care plans was only 50%. Though inhaled corticosteroids were deemed very safe or safe by 93%, almost half had specific concerns regarding at least 1 side effect, most commonly growth delay. Primary care physicians' criteria for referral to an asthma specialist differed from those of the NAEPP panel in choosing to manage more severe patients without asthma specialist input. Family physicians were more likely than pediatricians to refer a child after a single hospitalization, 2 to 3 emergency department visits, after 2 exacerbations, or if the child was <3 years old and required daily medications. Responses to vignettes showed generally appropriate initial use of antiinflammatory agents, but reluctance to increase the dose in response to continued symptoms, and less frequent follow-up than recommended by the NAEPP. CONCLUSION: Most physicians for children report having read and adopted NAEPP guideline recommendations for asthma treatment, including generally appropriate use of medications. Opportunities for improvement exist in specific areas such as the use of written care plans, optimizing antiinflammatory dosing, and providing routine follow-up. Although physicians show evidence of awareness of national guidelines and knowledge consistent with much of their content, additional work is required to promote the use of self-management tools in practice.
Administration, Inhalation↗
Postcystic development of Blastocystis hominis.
A concentrated suspension of Blastocystis hominis cysts was inoculated into Jones' medium and removed after 24 h for study of their development at the ultrastructural level. The parasite divides in the cyst, and up to three daughter cells can be seen. During this process the cyst wall dissolves, leaving behind thin membranous remnants. Excystation occurs mostly by the emergence of the daughter cells through an aperture in the outer fibrillar coat. Before excystation the vacuolar and the granular stages form and the daughter cells develop their own fibrillar layer.
Animals↗
Scanning electron microscopy of the surface coat of Blastocystis hominis.
Scanning electron microscopy of Blastocystis hominis showed that its outer coat has a fibrillar structure and individual fibrils may extend up to 5 microm from the periphery of the parasite. The surface coat remains intact during cell division. Bacteria are often seen adhering to it, but for the first time a trophozoite of Chilomastix mesnili was also seen in this position. It is postulated that breakdown of attached organisms may provide nutrients for Blastocystis.
Animals↗
Surgery of the salivary glands.
Surgery of the salivary glands evolved rapidly after a greater understanding of the anatomy and pathologic processes affecting them was achieved. This article reviews the general and neurovascular anatomy of the major salivary glands. Understanding the anatomy of the salivary glands is a cornerstone of competent salivary gland surgery. The surgical techniques, potential pitfalls of surgery, and avoidance of postsurgical complications have been highlighted. Recent advances in surgical techniques are also presented.
Humans↗
TRAF2 deficiency results in hyperactivity of certain TNFR1 signals and impairment of CD40-mediated responses.
Tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) can interact with various members of the TNF receptor family. Previously, we reported that TRAF2-deficient mice die prematurely and have elevated serum TNF levels. In this study, we demonstrate that TRAF2-deficient macrophages produce increased amounts of nitric oxide (NO) and TNF in response to TNF stimulation. Furthermore, we could enhance the survival of TRAF2-deficient mice by eliminating either TNF or TNFR1. Using these double-knockout mice, we show that in the absence of TRAF2, the T helper-dependent antibody response, CD40-mediated proliferation, and NF-kappaB activation are defective. These data demonstrate two important roles of TRAF2, one as a negative regulator of certain TNFR1 signals and the other as a positive mediator of CD40 signaling.
Animals↗
Expression of p21/waf1 in oral squamous cell carcinomas--correlation with p53 and mdm2 and cellular proliferation index.
The cyclin-dependent kinase inhibitor p21/waf1 is regulated by p53-dependent and p53-independent pathways. In addition, mdm2 is an oncogene which forms an auto-regulatory loop with the normal p53 protein and its role has been implicated in oncogenesis. To determine whether a correlation exists between the expression of these gene products, tumor differentiation, tumor staging and radiation therapy, we investigated the expression of p21, p53 and mdm2, and cellular proliferation by Ki-67 (MIB1) labeling index using immunohistochemistry in 88 human oral squamous cell carcinoma (SCC) samples from 56 patients. Tumor expression of all nuclear proteins was scored according to the percentage of positive cancer nuclei, both with the cancer tissue as a whole as well as in different epithelial compartments of differentiation. Positive p21, p53, mdm2 and MIB1 staining was present in 82.4, 67.8, 25.9 and 98.8% of the SCC samples. The staining in different epithelial compartments of differentiation varied: those of p21 and mdm2 present predominantly in suprabasal and upper regions of the tumors: those of p53 and MIB1 in basal and suprabasal regions. Higher levels of p21 expression were seen in actively proliferating tumors (P = 0.025). p21 expression positively correlated with mdm2 expression but not with p53 expression. Moreover, the level of p21 expression was higher in older patients (P = 0.024) and female patients (P = 0.008). There was no significant association among p53, mdm2 and MIB1. Expression of p53 was higher in tumors with poorer cellular differentiation and in younger patients (P = 0.038 and 0.028). There was no association between tumor stage by TNM classification and the expression of any of these gene products or proliferation index. Radiation therapy did not alter the expression of any of these. To conclude, p21 protein was overexpressed in oral SCCs, and this overexpression was related to cell proliferation index and mdm2 expression but independent of p53 protein alteration. Overexpression of p21 alone appeared to be insufficient to suppress tumor progression.
Adult↗
Effects of prognosis, perceived benefit, and decision style on decision making and critical care on decision making in critical care.
OBJECTIVE: To assess the effects of prognostic estimates, perceived benefit of treatment, and practice style on decision-making in critical care. DESIGN: Randomized assignment of subjects to either of two versions of a questionnaire designed to elicit treatment decisions for six intensive care unit cases based on actual patients. One version offered optimistic survival forecasts; the other, pessimistic forecasts. SUBJECTS: A random sample of 120 clinicians obtained from the Canadian Critical Care Society was contacted by mail. One version of the questionnaire was randomly assigned and mailed to each. Thirty-four replies, 17 for each version (response rate, 28%), were received and analyzed. MEASUREMENTS AND MAIN RESULTS: A list of treatment/management options was developed for each case, in three categories: recommended, questionable, and unacceptable. Subjects were also able to list new options that they would order that were not on the list. The dependent variables were the number of actions ordered in each category and the total for each case. Perceived benefit was measured by comparing subjective estimates of the probability of survival with the optimistic/pessimistic forecast given in the case. Practice style was assessed by correlating the total number of actions ordered across all possible pairs of cases. There were no significant differences between the two questionnaires on actions ordered either by category or by amount per category. Perceived benefit did not appear to be an important factor in decision-making. However, statistically significant correlations provide evidence for practice style in intensive care unit decision-making on an interventionist/noninterventionist dimension. CONCLUSIONS: There is no evidence that erroneous or biased prognostic estimates affect intensive care unit treatment choices. Neither the principle of maximizing expected utility nor the Rule of Rescue appear to affect these decisions systematically, but practice style does.
Canada↗