Working in management. Doctors do better financially than managers do.
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Humans↗
Biomedical subjects
S Hunter
Publications and source records attributed to S Hunter.
IT update/patient information. Fountain of knowledge.
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Computer Communication Networks↗
Inhibition of Fcgamma receptor-mediated phagocytosis by a nonphagocytic Fcgamma receptor.
There are three major classes of human Fcgamma receptors (FcgammaRI, FcgammaRII, and FcgammaRIII) and various isoforms of each class are capable of mediating phagocytosis. FcgammaRIIA is an unusual Fcgamma receptor in that it transmits a phagocytic signal in the absence of an additional receptor subunit. The cytoplasmic domain of FcgammaRIIA contains a conserved motif containing two copies of the sequence YXXL. The tyrosines (Y) within the motif are phosphorylated after receptor crosslinking and the integrity of these conserved sequences is required for efficient phagocytosis. The FcgammaRIIB receptors, FcgammaRIIB1 and FcgammaRIIB2, contain one copy of the cytoplasmic YXXL sequence and do not transmit a phagocytic signal. In B cells, FcgammaRIIB negatively regulates B-cell activation by the B-cell antigen receptor. Human macrophages express both FcgammaRIIA and FcgammaRIIB and while FcgammaRIIA mediates phagocytosis, the function of FcgammaRIIB in these cells is unknown. Using the epithelial/fibroblast-like cell line COS-1 as a model to examine the molecular events that regulate the phagocytosis of IgG-coated cells (EA), we investigated the effect of FcgammaRIIB on FcgammaRIIA signaling. FcgammaRIIB inhibited phagocytosis mediated both by FcgammaRIIA and by a chimeric FcgammaRIIA receptor containing the extracellular domain of FcgammaRI and the transmembrane and cytoplasmic domains of FcgammaRIIA. This inhibition occurred at an early signaling stage because tyrosine phosphorylation of the FcgammaRIIA cytoplasmic domain was inhibited after concurrent stimulation of these receptors with EA. FcgammaRIIB mutations showed the importance of the FcgammaRIIB YXXL for inhibition of FcgammaRIIA-mediated phagocytosis. Deletion of the FcgammaRIIB YXXL or conservative replacement of the YXXL tyrosine substantially reduced the inhibitory signal. FcgammaRIIB had a lesser inhibitory effect on phagocytosis by the Fcgamma receptor FcgammaRIIIA, which requires a gamma subunit to mediate a phagocytic signal. These results show that FcgammaRIIB negatively regulates phagocytic signaling by FcgammaRIIA and suggests that FcgammaRIIB plays a role in modulating FcgammaRIIA function in vivo.
Amino Acid Sequence↗
Pathology of hyalohyphomycosis caused by Scedosporium apiospermum (Pseudallescheria boydii): an emerging mycosis.
The genus Scedosporium contains two medically significant species of emerging mycotic agents, S. apiospermum and S. prolificans, which have received scant attention. Scedosporium apiospermum is the anamorph, or asexual state, of the cosmopolitan fungus Pseudallescheria boydii, with both sharing the same risk factors for infection, clinical spectrum, and histopathologic features. Scedosporium prolificans is a recently recognized agent of bone, soft tissue, and joint infections that occurs with highest frequency in children and young adults. S. prolificans may also cause potentially fatal disseminated infections in immunocompromised persons. The drug sensitivities of both Scedosporium species are significantly different from those of most other fungi, and thus identification of these organisms is important. Unfortunately, the pathological features of Scedosporium infections may be easily confused with other mycotic agents, resulting in delayed or inappropriate medical therapy. Because many pathologists and clinicians are unfamiliar with the significance of Scedosporium spp. infection, this communication describes three persons with differing clinical and pathological presentations of S. apiospermum infection. In one patient with sickle cell disease and chronic mycotic sinusitis, fungal colonies of S. apiospermum removed from the sinuses showed a pattern of alternating zones of mycelial hypercellularity and hypocellularity associated with conidiation, similar to a previous report of P. boydii infection. The clinicopathologic features of an immunocompetent person with S. apiospermum osteomyelitis, and a patient with S. apiospermum infection of the brain after bone marrow transplantation, are also described.
Adult↗
Techniques to evaluate elderly human muscle function: a physiological basis.
Elderly persons appear to exhibit muscle weakness and a slowing in their speed of muscle movement. Objective quantification of these characteristics requires reliable and practical tests to assess the muscle contractile characteristics of elderly people. This review discusses the advantages and limitations of voluntary and electrically stimulated muscle testing techniques used to assess the strength, speed, and fatigability of elderly muscle with a brief explanation of the physiological basis. This review presents the practice and theory underlying the scientific measurement of elderly human muscle function, bridging the gap between the practical issues of measurement and the physiological significance of such measurements.
Adult↗
Lipomatous glioneurocytoma of the posterior fossa with divergent differentiation: case report.
OBJECTIVE AND IMPORTANCE: We report a case of a posterior fossa neuroepithelial tumor with unusual clinical presentation, magnetic resonance imaging appearance, and morphological features. CLINICAL PRESENTATION: This 66-year-old man presented with a history of gait ataxia, dizziness, and tinnitus and was found to have a large tumor in the posterior fossa and cerebellopontine angle. INTERVENTION: Gross total excision of the tumor was accomplished. Histologically, the most unique features were macrovesicular accumulations of lipid, giving the tumor (at least focally) an appearance virtually identical to that of mature adipose tissue. Evidence of biphasic neuronal and glial differentiation was noted by immunohistochemistry and electron microscopy. CONCLUSION: A literature review is presented. Diagnostically, this neoplasm seems to fit in a unique group of rarely described, lipomatous neuroectodermal tumors that show divergent neuronal and glial differentiation.
Aged↗
Computerized analysis of restriction fragment length polymorphism patterns: comparative evaluation of two commercial software packages.
Two computerized restriction fragment length polymorphism pattern analysis systems, the BioImage system and the GelCompar system (Molecular Analyst Fingerprinting Plus in the United States), were compared. The two systems use different approaches to compare patterns from different gels. In GelCompar, a standard reference pattern in one gel is used to normalize subsequent gels containing lanes with the same reference pattern. In BioImage, the molecular sizes of the fragments are calculated from size standards present in each gel. The molecular size estimates obtained with the two systems for 12 restriction fragments of phage lambda were between 97 and 101% of their actual sizes, with a standard deviation of less than 1% of the average estimated size for most fragments. At the window sizes used for analysis, the GelCompar system performed somewhat better than BioImage in identifying visually identical patterns generated by electrophoretic separation of HhaI-restricted DNA of Listeria monocytogenes. Both systems require the user to make critical decisions in the analysis. It is very important to visually verify that the systems are finding all bands in each lane and that no artifacts are being detected; both systems allow manual editing. It is also important to verify results obtained in the pattern matching or clustering portions of the analysis.
Bacteriophage lambda↗
Your infection control program.
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HIV Infections↗
Binding of src-like kinases to the beta-subunit of the interleukin-3 receptor.
We have previously shown that stimulation of 32D cl3 cells with interleukin (IL)-3 results in the activation of three src-like tyrosine kinases, fyn, hck, and lyn. The beta subunit of the IL-3 receptor co-immunoprecipitated with hck in lysates of both unstimulated and IL-3-stimulated cells; however, the beta subunit did not precipitate with either fyn or lyn. The association of these three kinases with the beta subunit of the IL-3 receptor was further investigated using bacterial fusion proteins encoding the unique, SH3, and SH2 domains of these three kinases. Fusion proteins of both hck and fyn bound to a 150-kDa tyrosine-phosphorylated protein present in lysates of IL-3-stimulated cells. This protein was identified as the beta subunit of the IL-3 receptor by immunoblotting with an anti-beta antibody. Glutathione S-transferase (GST) fusion proteins containing the SH2 domain of hck bound to the beta subunit although the amount of beta subunit that bound to the SH2 domain alone was only 30% of that which bound to the fusion protein containing the unique, SH3, and SH2 domains. This indicates that the SH2 domain is one of the motifs involved in binding hck to the beta subunit. A GST fusion protein encoding a 236-amino acid region of the cytoplasmic tail of the beta subunit, which contained four tyrosine residues, bound to hck and fyn. Binding to both proteins was dramatically increased when the GST-beta fusion protein was tyrosine-phosphorylated. Far Western blot analysis was used to demonstrate the binding of the unique, SH3, and SH2 domains of hck to this 236-amino acid region of the beta subunit; tyrosine phosphorylation of this protein increased the binding of both the unique region and the SH2 domain probes. These data indicate that binding of hck to the beta subunit is mediated by both phosphotyrosine-dependent and -independent mechanisms.
Animals↗
Management of adults with congenital heart disease.
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Adult↗
Phosphorylation of cbl after stimulation of Nb2 cells with prolactin and its association with phosphatidylinositol 3-kinase.
Stimulation of Nb2 cells with PRL results in the rapid phosphorylation of a 120-kDa protein identified as the adapter protein cbl on tyrosine residues. Maximal phosphorylation of cbl occurs at 20 min after PRL stimulation and declines thereafter. Stimulation with as little as 5 nM PRL resulted in the phosphorylation of cbl; increasing the concentration of PRL to 100 nM had only a minimal effect upon the phosphorylation of cbl. The cbl protein appears to be constitutively associated with grb2 and the p85 subunit of phosphatidylinositol 3-kinase (PI 3-kinase). The constitutive association of cbl with the p85 subunit of PI 3-kinase was observed in Nb2 cells as well as in 32Dcl3 cells transfected with either the rat Nb2 (intermediate) form of the PRL receptor or the long form of the human PRL receptor. A glutathione S-transferase fusion protein encoding the SH3 domain of the p85 subunit of PI 3-kinase bound to cbl in lysates of both unstimulated and PRL-stimulated Nb2 cells; however, neither of the SH2 domains of p85 bound to cbl under the same conditions. PRL stimulation increased the cbl-associated PI kinase activity. The majority of PI kinase activity appeared to be cbl-associated after PRL stimulation. These results suggest that cbl may function as an adapter protein in PRL-mediated signaling events and regulate activation of PI 3-kinase. Our model suggests that the p85 subunit of PI 3-kinase is constitutively associated with cbl through binding of the p85 SH3 domain to a proline-rich sequence in cbl. After the tyrosine phosphorylation of cbl, an SH2 domain(s) of p85 binds to a specific phosphorylation site(s) in cbl, leading to the activation of PI 3-kinase.
Adaptor Proteins, Signal Transducing↗
A case of acute monocytic ehrlichiosis with prominent neurologic signs.
Human monocytic ehrlichiosis is a recently described tick-borne infection with the rickettsial organism Ehrlichia chaffeensis. We describe a patient with documented E chaffeensis infection and multiple organ system involvement. Prominent neurologic symptoms and signs included severe headache, meningismus, and altered mental status. Additional neurologic findings included unilateral arm weakness and a Bell's palsy. Biopsy of brain and meninges demonstrated an infiltrate of atypical lymphoid cells in the leptomeninges with involvement of blood vessel walls and extension into the Virchow-Robin spaces. Bone marrow biopsy revealed fibrin-ringed granulomas. The patient also developed a nonspecific increase in immunoglobulin production. Host immune response may play a critical role in the pathophysiology of ehrlichiosis.
Biopsy↗
Using rapid research to develop a national strategy to assist families affected by AIDS in Tanzania.
Although information on African family adaptation to the AIDS epidemic is critical to planning and managing government, donor and NGO programs of assistance, current knowledge is limited to a small number of research studies. An AIDS prevention project in Tanzania undertook a rapid national assessment to identify the major problems for families in Tanzania in adapting to the epidemic. The methodology used for the work was distinct from prior studies: the research covered a wide cross-section of Tanzanian population groups to gauge the extent of ethnic, urban-rural and regional variation; it was rapid and qualitative, to gather data on broad trends in a short time; and it was designed in co-operation with policy-makers so they could understand the approach being used and were receptive to the findings. The study identified common problems in AIDS care, counselling and survivor assistance. Many of the problems for families with AIDS have their origin in poverty and changes in African family structures over the past 20 years, which African demographers are just beginning to describe. Stresses arising from these changes are now being aggravated by AIDS, but families with sufficient resources, whether female or male-headed, are coping better than those without.
Acquired Immunodeficiency Syndrome↗
Comparison of the effects of the interposition of 'narrow' cycloperistaltic v. antiperistaltic segments on fluid perfusion through isolated loops of jejunum.
Experimental studies in dogs showed a delaying action of the cycloperistaltic (C-P) segment when interposed in isolated loops of jejunum ('narrow' C-P segments) and between stomach and duodenum after Billroth I gastrectomies ('wide' C-P segments). This study was designed to establish whether there were any differences in the delaying action on the passage of perfused fluids between isolated loops of jejunum with C-P and antiperistaltic (A-P) segments interposed. The latter is the surgical technique that is currently considered the gold standard for such actions. Two isolated segments of jejunum with the ends exteriorised as jejunostomies (Thiry-Vella (T-V) loops) were created in each of 4 dogs. Towards the end of one, a C-P segment with a diameter 70% that of the jejunum ('narrow' C-P segment) was interposed. Towards the end of the other, a reversed A-P segment was interposed. Fluid containing 14C-labelled polyethylene glycol was infused at a rate of 4 ml/min through all the 8 loops (4 dogs) for 1 hour (6 experiments per dog). Descriptive statistics (means and standard errors) show that no obvious differences in volume of output, absorption and pooling existed between T-V loops with 'narrow' C-P and A-P segments. The delaying effect in the passage of fluids of the C-P segment, shown in previous experiments, does not appear to be superior to that of the A-P segment. This statement is made with some reservation as the number of animals involved was relatively small and analytical statistics could not be used.
Animals↗
Pressure ulcer incidence in an acute care setting.
The purpose of this prospective study was to determine the incidence of pressure ulcers and to examine factors related to pressure ulcer development in patients in an acute care setting. Adult medical and surgical patients who were free of pressure ulcers at admission were assessed within 36 hours of admission and then three times per week for 2 weeks or until discharge. Instruments included a demographic data form, a skin assessment form, and the Braden Scale for Predicting Pressure Sore Risk. Most subjects had 46 assessments completed. The sample consisted of 149 subjects, with a pressure ulcer incidence rate of 13.4% (n = 20). Subjects who acquired pressure ulcers had lower hemoglobin levels (t = 2.17, p = 0.03), spent more time in bed (t = 3.90, p = 0.0001), and spent less time in a chair (t = 3.2, p = 0.002) than those who did not acquire pressure ulcers. A stepwise logistic regression analysis was used to calculate risk of pressure ulcer development. In the final model, hemoglobin level and hours spent in bed continued to be predictors of pressure ulcer development (chi 2 = 9.306, df = 2, p = 0.0095). All 20 subjects who acquired pressure ulcers were further categorized into groups with stage I (n = 12) or stage II (n = 8) ulcers. Patients with stage I pressure ulcers were primarily receiving post-surgical care (67%), whereas patients who acquired stage II ulcers had medical conditions that affected tissue perfusion, such as respiratory diseases (50%) and diabetes mellitus (12%).
Acute Disease↗
Protective effects of calcium from nonfat dried milk against colon carcinogenesis in rats.
A number of studies have demonstrated the protective effect of dietary calcium against risk for colon cancer. The objective of this experimental study was to test the efficacy of two sources of dietary calcium, elemental calcium in the form of CaCO3 and dairy calcium as nonfat dried milk (NFDM), in colon tumor inhibition. Male weanling F344 rats were fed six test diets containing low (LF, 5%) and high (HF, 20%) levels of corn oil and low (0.5%) and high (1.0%) levels of calcium supplemented as CaCO3 or NFDM in a 2 x 3 factorial design. Tumors were induced with two weekly injections of azoxymethane at 12 mg/kg body wt. After 27 weeks on the test diets, animals were necropsied for tumor analysis. There was no difference in tumor incidence for fat or calcium source main effects, but a significant interaction was seen between fat and calcium source, with the lowest tumor incidence seen in the HF/NFDM group. Calcium compartmentalization studies demonstrated no effects of calcium on serum calcium levels but increased urinary and fecal water calcium in the higher-calcium diets. Increased dietary calcium also decreased fecal bile acid concentrations, but there was no effect on fecal water bile acids. Intermediate biomarkers of colon carcinogenesis were not affected by the dietary treatments except for fat effects on carcinogen-induced nuclear aberrations. These results indicate that source of calcium is not critical but that total dietary context may affect efficacy of calcium against colon carcinogenesis.
Animals↗
Abrogation of the Fc gamma receptor IIA-mediated phagocytic signal by stem-loop Syk antisense oligonucleotides.
The role of Syk kinase in Fc gamma receptor (Fc gamma R) IIA-mediated phagocytosis was examined with two forms of antisense oligodeoxynucleotides (ODNs) designed to hybridize to human Syk mRNA. Monocytes were incubated with linear and stem-loop antisense ODNs targeted to Syk mRNA. When complexed with cationic liposomes, stem-loop Syk antisense ODN with phosphorothioate modification exhibited stability in fetal bovine and human serum. The stem-loop Syk antisense ODN at a concentration of 0.2 microM inhibited Fc gamma RIIA-mediated phagocytosis by 90% and completely eliminated Syk mRNA and protein in monocytes, whereas scrambled-control ODNs had no effect. The Syk antisense ODNs did not change beta-actin mRNA levels and Fc gamma RII cell-surface expression. In addition, stem-loop Syk antisense ODN inhibited Fc gamma RI and Fc gamma RIIIA-mediated phagocytosis. These data indicate the efficacy of stem-loop Syk antisense ODN for targeting and degrading Syk mRNA and protein and the importance of Syk kinase in Fc gamma receptor-mediated phagocytosis. Immunoblotting assay demonstrated that Fc gamma RII tyrosine phosphorylation after Fc gamma RII cross-linking did not change in the absence of Syk protein. These results indicate that Syk kinase is required for Fc gamma RIIA-mediated phagocytic signaling and that Fc gamma RII cross-linking leads to tyrosine phosphorylation of Fc gamma RII independent of Syk kinase.
Animals↗
Decreasing the prevalence of pressure ulcers using agency standards.
Home care patients either have or are at high risk for pressure ulcers. This article describes the outcome of a study that examined the effects of pressure ulcer prevention and treatment standards on the prevalence rate of a home healthcare agency's client caseload. Implications for practice and further research also are discussed.
Adolescent↗