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101.
Nahid Tayebi David Q. Andrews Joseph K. Park Eduard Orvisky John McReynolds Donna M. Krasnewich 《American journal of medical genetics. Part A》2002,108(3):241-246
Congenital disorders of glycosylation (CDG) are a group of metabolic disorders with multisystemic involvement characterized by abnormalities in the synthesis of N‐linked oligosaccharides. The most common form, CDG‐Ia, resulting from mutations in the gene encoding the enzyme phosphomannomutase (PMM2), manifests with severe abnormalities in psychomotor development, dysmorphic features and visceral involvement. While this disorder is panethnic, we present the first cases of CDG‐Ia identified in an African American family with two affected sisters. The proband had failure to thrive in infancy, hypotonia, ataxia, cerebellar hypoplasia and developmental delay. On examination, she also exhibited strabismus, inverted nipples and an atypical perineal fat distribution, all features characteristic of CDG‐Ia. Direct sequencing demonstrated that the patient had a unique genotype, T237M/c.565‐571 delAGAGAT insGTGGATTTCC. The novel deletion–insertion mutation, which was confirmed by subcloning and sequencing of each allele, introduces a stop codon 11 amino acids downstream from the site of the deletion. The presence of this deletion–insertion mutation at cDNA position 565 suggests that this site in the PMM2 gene may be a hotspot for chromosomal breakage. Published 2002 Wiley‐Liss, Inc. 相似文献
102.
Jian Huang Herbert Yu Estela Marin Stephanie Brock Donna Carden Terry Davis 《Academic medicine》2004,79(2):156-161
PURPOSE: Primary care physicians are an important source of information on weight management. Nevertheless, weight loss counseling by these physicians remains inadequate. This study sought to determine physicians' barriers to providing weight loss counseling in a public hospital, patients' recall of physicians' weight loss recommendations, and the influence of physicians' counseling on patients' understanding, motivation, and behavior regarding weight loss. METHOD: In 2001, four focus groups of faculty and residents were held at two primary care clinics affiliated with the Louisiana State University Health Sciences Center-Shreveport to determine the barriers to providing weight loss counseling. Scripted probes were used to uncover consensus norms. In 2001-02, structured exit interviews were conducted with 210 overweight or obese patients recruited from the clinics to determine patients' recall of physicians' weight loss recommendations, and patients' understanding of the relationship between weight and health, and their stages of readiness for weight loss. RESULTS: Physicians identified major barriers to providing weight loss counseling, including insufficient confidence, knowledge, and skills. Obesity was underdocumented as a distinct clinical diagnosis. Only 5% of the patients recalled being given the combined weight loss strategy of diet and exercise. However, patients who recalled being counseled to lose weight were more likely to understand the risks of obesity, the benefits of weight loss, and were at a higher stage of readiness for weight loss. CONCLUSIONS: Physicians' weight loss counseling had a significant effect on patients' understanding of and motivation for weight loss. However, physicians provided insufficient guidance on weight management strategies, possibly because of inadequate counseling skills and confidence. 相似文献
103.
Safe medication prescribing: training and experience of medical students and housestaff at a large teaching hospital. 总被引:2,自引:0,他引:2
Jane M Garbutt Gabrielle Highstein Donna B Jeffe William Claiborne Dunagan Victoria J Fraser 《Academic medicine》2005,80(6):594-599
PURPOSE: To assess medical students' and housestaff's knowledge, attitudes, and behaviors regarding safe prescribing. METHOD: In 2003, 214 housestaff (interns and residents) and 77 medical students in medicine and surgery at Barnes-Jewish Hospital, St. Louis, Missouri, were asked to complete an anonymous, self-administered questionnaire about safe prescribing. Questions asked about training in and attitudes about safe-prescribing and current prescribing behaviors. Fisher exact test was used to compare attitudes and behaviors among subgroups. RESULTS: Of the 175 (60%) respondents, 73 (59%) of 123 housestaff and eight (15%) of 52 students agreed that their safe-prescribing training was adequate (p < .001), and 145 (83%) total respondents agreed that prescribing errors were unacceptable. Respondents reported always doing the following: 156 (89%) checked prescribing information before prescribing new drugs, 131 (75%) checked for drug allergies, 103 (59%) double-checked dosage calculations, 98 (56%) checked for renal impairment, and 53 (30%) checked for potential drug-drug interactions. CONCLUSION: Routine use of safe medication prescribing behaviors among housestaff and medical students was poor. Contributing factors may have included inadequate training and a culture that does not support safe prescribing. Effective strategies to increase safe medication prescribing need to be identified and implemented. 相似文献
104.
Salmena L Lemmers B Hakem A Matysiak-Zablocki E Murakami K Au PY Berry DM Tamblyn L Shehabeldin A Migon E Wakeham A Bouchard D Yeh WC McGlade JC Ohashi PS Hakem R 《Genes & development》2003,17(7):883-895
Defects in death receptor-mediated apoptosis have been linked to cancer and autoimmune disease in humans. The in vivo role of caspase 8, a component of this pathway, has eluded analysis in postnatal tissues because of the lack of an appropriate animal model. Targeted disruption of caspase 8 is lethal in utero. We generated mice with a targeted caspase 8 mutation that is restricted to the T-cell lineage. Despite normal thymocyte development in the absence of caspase 8, we observed a marked decrease in the number of peripheral T-cells and impaired T-cell response ex vivo to activation stimuli. caspase 8 ablation protected thymocytes and activated T-cells from CD95 ligand but not anti-CD3-induced apoptosis, or apoptosis activated by agents that are known to act through the mitochondria. caspase 8 mutant mice were unable to mount an immune response to viral infection, indicating that caspase 8 deletion in T-cells leads to immunodeficiency. These findings identify an essential, cell-stage-specific role for caspase 8 in T-cell homeostasis and T-cell-mediated immunity. This is consistent with the recent identification of caspase 8 mutations in human immunodeficiency. 相似文献
105.
Gordon M. Dickinson Timothy J. Cleary Tamara Sanderson Michael R. McGinnis 《Journal of clinical microbiology》1983,17(1):155-158
A case of subcutaneous phaeohyphomycosis in a human, involving the ankle and caused by Scytalidium lignicola, is described. The isolate was found to be sensitive to amphotericin B, 5-fluorocytosine, miconazole, and ketoconazole in vitro. 相似文献
106.
Ganta SR Piesco NP Long P Gassner R Motta LF Papworth GD Stolz DB Watkins SC Agarwal S 《Journal of biomedical materials research. Part A》2003,64(2):242-248
Urethanes are frequently used in biomedical applications because of their excellent biocompatibility. However, their use has been limited to bioresistant polyurethanes. The aim of this study was to develop a nontoxic biodegradable polyurethane and to test its potential for tissue compatibility. A matrix was synthesized with pentane diisocyanate (PDI) as a hard segment and sucrose as a hydroxyl group donor to obtain a microtextured spongy urethane matrix. The matrix was biodegradable in an aqueous solution at 37 degrees C in vitro as well as in vivo. The polymer was mechanically stable at body temperatures and exhibited a glass transition temperature (Tg) of 67 degrees C. The porosity of the polymer network was between 10 and 2000 microm, with the majority of pores between 100 and 300 microm in diameter. This porosity was found to be adequate to support the adherence and proliferation of bone-marrow stromal cells (BMSC) and chondrocytes in vitro. The degradation products of the polymer were nontoxic to cells in vitro. Subdermal implants of the PDI-sucrose matrix did not exhibit toxicity in vivo and did not induce an acute inflammatory response in the host. However, some foreign-body giant cells did accumulate around the polymer and in its pores, suggesting its degradation is facilitated by hydrolysis as well as by giant cells. More important, subdermal implants of the polymer allowed marked infiltration of vascular and connective tissue, suggesting the free flow of fluids and nutrients in the implants. Because of the flexibility of the mechanical strength that can be obtained in urethanes and because of the ease with which a porous microtexture can be achieved, this matrix may be useful in many tissue-engineering applications. 相似文献
107.
1. The cardiac sac motor pattern consists of slow and irregular impulse bursts in the motor neurons [cardiac sac dilator 1 and 2 (CD1 and CD2)] that innervate the dilator muscles of the cardiac sac region of the crustacean foregut. 2. The effects of the peptides, proctolin and red pigment-concentrating hormone (RPCH), on the cardiac sac motor patterns produced by in vitro preparations of the combined stomatogastric nervous system [the stomatogastric ganglion (STG), the paired commissural ganglia (CGs), and the oesophageal ganglion (OG)] were studied. 3. Bath applications of either RPCH or proctolin activated the cardiac sac motor pattern when this motor pattern was not already active and increased the frequency of the cardiac sac motor pattern in slowly active preparations. 4. The somata of CD1 and CD2 are located in the esophageal and stomatogastric ganglia, respectively. Both neurons project to all four of the ganglia of the stomatogastric nervous system. RPCH elicited cardiac sac motor patterns when applied to any region of the stomatogastric nervous system, suggesting a distributed pattern generating network with multiple sites of modulation. 5. The anterior median (AM) neuron innervates the constrictor muscles of the cardiac sac. The AM usually functions as a part of the gastric mill pattern generator. However, when the cardiac sac is activated by RPCH applied to the stomatogastric ganglion, the AM neuron becomes active in antiphase with the cardiac sac dilator bursts. This converts the cardiac sac motor pattern from a one-phase rhythm to a two-phase rhythm. 6. These data show that a neuropeptide can cause a neuronal element to switch from being solely a component of one neuronal circuit to functioning in a second one as well. This example shows that peptidergic "reconfiguration" of neuronal networks can produce substantial changes in the behavior of associated neurons. 相似文献
108.
Carlson EC Audette JL Veitenheimer NJ Risan JA Laturnus DI Epstein PN 《The anatomical record. Part A, Discoveries in molecular, cellular, and evolutionary biology》2003,271(2):332-341
Capillary basement membrane (CBM) thickening is an ultrastructural hallmark in diabetic patients and in animal models of diabetes. However, the wide variety of tissues sampled and diverse methods employed have made the interpretation of thickness data difficult. We showed previously that acellular glomerular BMs in OVE26 transgenic diabetic mice were thickened beyond normal age-related thickening, and in the current study we hypothesized that other microvascular BMs likewise would show increased widths relative to age-matched controls. Accordingly, a series of tissues, including skeletal and cardiac muscle, ocular retina and choriod, peripheral nerve, lung, pancreas, and renal glomerulus was collected from 300-350-day-old normal and transgenic mice. Transmission electron micrographs of cross sections through capillary walls were prepared, and CBM thickness (CBMT) was determined by the "orthogonal intercept" method. Morphometric analyses showed highly variable transgene-related BMT increases in the sampled tissues, with glomerular BM showing by far the greatest increase (+87%). Significant thickness increases were also seen in the retina, pulmonary alveolus, and thoracoabdominal diaphragm. BMT increases were not universal; however, most were modestly widened, and those that were thickest in controls generally showed the greatest increase. Although the pathogenesis of diabetes-related increases in CBM is poorly understood, data in the current study showed that in OVE26 transgenic mice increased BMT was a frequent concomitant of hyperglycemia. Accordingly, it seems likely that hyperglycemia-induced microvascular damage may be a contributing factor in diabetic BM disease, and that microvessel cellular and extracellular heterogeneity may limit the extent of CBM thickening in diverse tissues. 相似文献
109.
110.
Donald Y. M. Leung MD PhD Donna M. Ambrosino MD Robert D. Arbeit MD Julie L. Newton BS Raif S. Geha MD 《The Journal of allergy and clinical immunology》1988,81(6):1082-1087
Patients with the hyper-IgE (HIE) syndrome have recurrent bacterial infections with Staphylococcus aureus and other polysaccharide encapsulated organisms. To determine whether an impairment of the antibody response to polysaccharide antigens contributes to infections in this syndrome, we measured serum antibody to the teichoic acid of S. aureus and to the capsular polysaccharide of Haemophilus influenzae type b. Compared to control subjects who had no history of S. aureus infections (N = 14), sera from patients with HIE (N = 9) lacked the expected elevation of serum antibody to teichoic acid (p greater than 0.05) and had significantly lower levels of this antibody than sera from 14 patients with atopic dermatitis, complicated by recurrent cutaneous S. aureus infections (p less than 0.01). After immunization with the capsular polysaccharide of Haemophilus influenzae type of vaccine, the antibody response of patients with HIE was significantly impaired compared to that of age-matched control subjects (p = 0.01). Although patients with HIE syndrome had normal total IgG levels, most patients with HIE but not patients with atopic dermatitis had IgG2 subclass deficiency. Defective antibody responses in patients with HIE were not restricted to polysaccharide antigens because the serum levels of antitetanus toxoid antibody in these patients were significantly lower than that of control subjects (p less than 0.001). Impaired antigen-specific antibody responses in patients with HIE syndrome may contribute to their increased susceptibility to infection. 相似文献