Biomedical subjects
Publications and source records attributed to J Jackson.
The receptive and expressive language skills of 10 children with strokes due to sickle cell disease were significantly poorer than those of their matched controls. The children with strokes had greatest difficulty in following oral directions and formulating sentences.
1. Patients who demonstrate self-wounding behaviour require behavioral, pharmacological, and psychotherapeutic interventions to meet their highly complex needs. 2. Nurses caring for patients who wound themselves will experience frustration related to the safety needs of the patients and guilt whenever an injury occurs. 3. Staff members managing the patient who wounds himself or herself need administrative support, education, and counseling to relieve guilt, personal and professional conflict, and stress.
BACKGROUND: A correct balance between protease and inhibitor activity is critical in the maintenance of homoeostasis; excessive activation of enzyme pathways is frequently associated with inflammatory disorders. Plasmin is an enzyme ubiquitously activated in inflammatory disorder, and C1-inhibitor (C1-Inh) is a pivotal inhibitor of protease activity, which is particularly important in the regulation of enzyme cascades generated in plasma. The nature of the interaction between plasmin and C1-Inh is poorly understood. MATERIALS AND METHODS: C1-Inh was immunoadsorbed from the plasma of normal individuals (n = 21), from that of patients with systemic lupus erythematosus (n = 18) or adult respiratory distress syndrome (n = 9), and from the plasma and synovial fluid of patients with rheumatoid arthritis (n = 18). As plasmin is a putative enzyme responsible for C1-Inh was examined using SDS-PAGE. In addition, peptides cleaved from C1-Inh by plasmin were isolated and sequenced and the precise cleavage sites determined from the known primary sequence of C1-Inh. Homology models of C1-Inh were then constructed. RESULTS: Increased levels of cleaved and inactivated C1-Inh were found in each of the inflammatory disorders examined. Through SDS-PAGE analysis it was shown that plasmin rapidly degraded C1-Inh in vitro. The pattern of C1-Inh cleavage seen in vivo in patients with inflammatory disorders and that produced in vitro following incubation with plasmin were very similar. Homology models of C1-Inh indicate that the majority of the plasmin cleavage sites are adjacent to the reactive site of the inhibitor. CONCLUSIONS: This study suggests that local C1-Inh degradation by plasmin may be a central and critical event in the loss of protease inhibition during inflammation. These findings have important implications for our understanding of pathogenic mechanisms in inflammation and for the development of more effectively targeted therapeutic regimes. These findings may also explain the efficacy of anti-plasmin agents in the treatment of C1-Inh deficiency states, as they may diminish plasmin-mediated C1-Inh degradation.
Metastatic Lewis lung carcinoma (LLC-LN7) variants have previously been shown to have reduced levels of protein phosphatase-2A (PP-2A) activity as compared to the nonmetastatic LLC-C8 cells. The present study showed that inhibition of PP-2A in the nonmetastatic LLC-C8 cells caused a rapid change from a spread to a rounded morphology and increased their in vitro invasiveness through laminin. In contrast, the metastatic LLC-LN7 cells were rounded and invasive, which was not affected by inhibition of PP-2A. To determine whether these differences could be attributed to alterations in PP-2A association with the cytoskeleton, the extent of PP-2A colocalization with microtubules was tested. Immunostaining for tubulin showed prominent filamentous fibers in nonmetastatic LLC-C8 cells and small foci of PP-2A immunostaining along these microtubules. In contrast, the tubulin staining was diffuse throughout the metastatic LLC-LN7 cells and there was little evidence of association with PP-2A. Western blot analyses showed that this reduced level of PP-2A association with microtubules in metastatic LLC-LN7 cells was not due to differences in levels of the PP-2A subunits. Instead, it may be due to the reduced association of the subunits into the heterotrimeric form of the PP-2A holoenzyme. These studies show the importance of PP-2A in maintaining a spread morphology and in restricting invasiveness, and a loss of this regulatory control in metastatic cells. This loss of PP-2A regulatory control in metastatic cells may be due to a reduction in the trimeric form of the PP-2A holoenzyme.
Human acute phase serum amyloid A (the A-SAA2 isoform) was expressed at high levels using the pGEX bacterial expression system. A-SAA2 protein was expressed in E. coli NM544 as part of a fusion protein facilitating rapid purification. A-SAA2 was cleaved from the fusion moiety in the presence of a non-ionic detergent (Triton X-100) to release a soluble A-SAA2. Further purification using ion exchange chromatography yielded a pure A-SAA2 (3 mg per litre of culture). Antibodies generated against recombinant A-SAA2 were specific for the acute phase SAAs, A-SAA1 and A-SAA2 and showed no cross-reactivity with the constitutively expressed SAA (C-SAA). These antibodies were used to develop a rapid enzyme-linked immunosorbent assay (ELISA) specific for the measurement of A-SAA in serum.
Antibodies reactive with cytoplasmic components of neutrophils (ANCA) have received much attention because of their association with vasculitis and other inflammatory disorders. In this study, ELISA and immunofluorescence assays were employed to detect antimonocyte-specific antibodies and similar assays were used in parallel to detect anti-neutrophil cytoplasmic antibodies in a range of patient sera: Wegener's granulomatosis (14), Crohn's disease (46), ulcerative colitis (43), sarcoidosis (40), rheumatoid factor positive (15), and normal controls (22). Using an ELISA, anti-monocyte antibodies were detected in (figures in parentheses represent anti-neutrophil results): Wegener's granulomatosis, 79% (93%); sarcoidosis, 30% (5%); Crohn's disease, 20% (11%); ulcerative colitis, 0% (49%); rheumatoid factor-positive sera, 0% (0%). Excellent concordance (>98%) was found between the ELISA and immunofluorescence assays and all of the anti-monocyte antibodies gave a cytoplasmic pattern of staining. This is the first report demonstrating the presence of antibodies specific to the cytoplasmic components of monocytes in patients with granulomatous disease and these findings enhance our understanding of auto-antibody responses against phagocytic cell components.
BACKGROUND: Failure of high-level disinfection of bronchoscopes has caused several outbreaks of nosocomial infection or pseudoinfection involving mycobacteria. METHODS: Inocula (10(5) colony-forming units/ml and 10(8) colony-forming units/ml) of a clinical Mycobacterium gordonae isolate were used to contaminate bronchoscopes. Glutaraldehyde, iodophor, and peracetic acid disinfectants were evaluated in manual and automated disinfection procedures after 10- to 20-minute exposures at 20 degrees and > or = 25 degrees C. RESULTS: Four of five manual disinfectant procedures failed to eliminate experimental M. gordonae infection after 10-minute exposure at 20 degrees C. All five manual procedures tested at 20 degrees C were effective after 20-minute exposure to the five disinfectants (two 2% alkaline glutaraldehyde preparations, 3.2% alkaline glutaraldehyde, 75 ppm iodophor, and 0.5% glutaraldehyde-0.03% phenolic). Three of four manual (one 2% glutaraldehyde, 3.2% glutaraldehyde, and 0.5% glutaraldehyde-0.03% phenolic) and three automated (one 2% glutaraldehyde, 0.5% glutaraldehyde-0.03% phenolic, and 0.2% peracetic acid) disinfectant procedures eliminated contamination after a 10- to 12-minute exposure at > or = 25 degrees C. Effective total cycle times for the three automated procedures ranged from 20 to 45 minutes. CONCLUSIONS: Previously Environmental Protection Agency-approved tuberculocidal agents may be ineffective against M. gordonae when used according to label claims under normal clinical conditions. A minimum 20-minute exposure time at 20 degrees C is necessary for manual disinfection methods. Higher temperatures may improve disinfectant efficacy. Newer automatic disinfection machines may be as effective as traditional manual methods and also may reduce hazards to employees.
In 1960, progressive sensorineural deafness (McKusick 304,700, DFN-1) was shown to be X-linked based on a description of a large Norwegian pedigree. More recently, it was shown that this original DFN-1 family represented a new type of recessive neurodegenerative syndrome characterized by postlingual progressive sensorineural deafness as the first presenting symptom in early childhood, followed by progressive dystonia, spasticity, dysphagia, mental deterioration, paranoia and cortical blindness. This new disorder, termed Mohr-Tranebjaerg syndrome (referred to here as DFN-1/MTS) was mapped to the Xq21.3-Xq22 region2. Using positional information from a patient with a 21-kb deletion in chromosome Xq22 and sensorineural deafness along with dystonia, we characterized a novel transcript lying within the deletion as a candidate for this complex syndrome. We now report small deletions in this candidate gene in the original DFN-1/MTS family, and in a family with deafness, dystonia and mental deficiency but not blindness. This gene, named DDP (deafness/ dystonia peptide), shows high levels of expression in fetal and adult brain. The DDP protein demonstrates striking similarity to a predicted Schizosaccharomyces pombe protein of no known function. Thus, is it likely that the DDP gene encodes an evolutionarily conserved novel polypeptide necessary for normal human neurological development.
OBJECTIVES: We treated the hypothesis that heatstroke is associated with endothelial cell activation/injury and examined the possibility that the markers of endothelial cell activation/injury may be associated with its severity and complications such as disseminated intravascular coagulation, lung injury, and renal dysfunction. DESIGN: Prospective analyses. SETTING: Heatstroke Center in Makkah, Saudi Arabia. PATIENTS: Twenty-two adult patients with heatstroke. INTERVENTIONS: The plasma concentration of endothelin, circulating intercellular adhesion molecule-1 (ICAM-1), and von Willebrand factor-antigen values were measured, respectively, by radioimmunoassay, enzyme-linked immunosorbent assay, and rocket electroimmunoassay, in heatstroke patients on admission (precooling) and after complete cooling (postcooling), and in ten normal control patients. MEASUREMENTS AND MAIN RESULTS: Precooling heatstroke patients (rectal temperature 40.9 +/- 1.1 [SD] degrees C) had increased circulating concentrations of endothelin, c-ICAM-1, and von Willebrand factor-antigen in 100%, 80%, and 77% of patients to 126.4 +/- 11.2 pmol/L, 523.1 +/- 154.4 ng/mL, and 3.85 +/- 2.3 U/mL, respectively (control values: 13.7 +/- 4.2 pmol/L [p < .001]; 247.4 +/- 68.2 ng/ml [p < .001]; and < 1.5 U/mL, respectively). There was a significant (r2 = .68, p < .01) correlation between circulating ICAM-1 and endothelin concentrations. Plasma endothelin concentration correlated negatively with temperature (r2 = .35, p < .05). Mean endothelin concentration was similar in patients with or without renal dysfunction, and mean von Willebrand factor-antigen concentration was similar in patients with or without lung injury or disseminated intravascular coagulation. There were no significant correlations between circulating ICAM-1, endothelin, or von Willebrand factor-antigen concentration and the Simplified Acute Physiology core. After cooling, mean circulating ICAM-1 and endothelin concentrations decreased significantly to 400 +/- 109 ng/mL and 93 +/- 38.5 pmol/L, respectively, whereas the mean von Willebrand factor-antigen concentration increased to 5.55 +/- 2.18 U/mL (p > .05). CONCLUSIONS: Our findings of increased circulating concentrations of circulating ICAM-1, endothelin, and von Willebrand factor-antigen are consistent with the hypothesis that heatstroke is associated with endothelial cell activation/injury. Whether the endothelial cell activation/injury is implicated in the pathophysiology of this disorder merits further studies.
C1-inhibitor (C1-Inh) is a serine esterase proteinase inhibitor (serpin) which plays an important role in regulating serine proteinases of the early inflammatory response. In this study, we describe a novel and versatile polyclonal antibody capture assay to examine C1-Inh consumption in vivo. This assay has advantages over previously described methods of measuring C1-Inh consumption as it allows the assessment of the relative amounts of native, complexed and cleaved inhibitor circulating in plasma. By using polyclonal antibodies specific for other complement proteins, the C1-Inh capture assay was adapted to measure in vivo activation of C3, C4 and factor B. C1-Inh consumption and complement activation were examined in the plasma of 21 normal individuals, 24 individuals with systemic lupus erythematosus (SLE), nine individuals with adult respiratory distress syndrome (ARDS) and in the paired plasma and synovial fluid from 18 patients with rheumatoid arthritis (RA). The C1-Inh capture assay revealed native, cleaved and complexed C1-Inh migrating at 115 kDa, 96 kDa and 209-225 kDa respectively, in normal plasma. C1-Inh consumption was increased in the plasma of all the inflammatory disorders examined, in comparison to normal plasma. It is proposed that this serpin capture assay could be adapted to the study of serpin involvement in a wide variety of inflammatory disorders.
With more than 25,000 professional nurse members, the Oncology Nursing Society (ONS) is the largest oncology membership organization in the world. Now in its 20th year, one way that ONS supports its mission of promoting excellence in oncology nursing is through the development and dissemination of patient care standards and guidelines. The first guidelines to be developed by ONS were the Cancer Chemotherapy Guidelines. Now in their third edition, the historical development and revision of these guidelines is detailed in this article, along with the evaluation and refinement of the process utilized by ONS.
Data for 473 African-American and white smokers showed that whites were more likely than African Americans to use formal cessation programs to quit smoking, to report that their doctor told them to stop smoking, and to use nicotine replacement therapy. While physicians advised a high proportion of smokers of each race group to quit smoking and were quite aggressive in prescribing nicotine replacement therapy, they were deficient in providing necessary behavioral support to their patients.
In order to improve the effectiveness and subtainability of the family planning programme, the National Family Planning Board has devised a strategy to shift users to longer-acting methods and increase the role of the private sector. To design interventions, a better understanding of existing services was thought to be necessary. This study examines the distribution of family planning service delivery points in Jamaica and the services offered by the public and private sectors through an examination of records and questionnaire interviews. The study found that, because of the concentration of private sector providers-the main outlets for longer-acting methods-in urban areas, rural areas had poor access to these methods. Because rural areas are not attractive to private sector providers, the public sector should recognize the need to continue to serve these areas.
OBJECTIVE: Will a program using biofeedback help patients with post radical prostatectomy incontinence to achieve continence by increasing their ability to contract pelvic floor muscles? STUDY DESIGN: Twenty-seven patients who had undergone incontinent radical prostatectomy were evaluated for urinary incontinence and treated at the Urology Biofeedback Laboratory at our institution. Patients were assessed by urodynamic studies including uroflow, postvoid residual measurement, and cystometrogram before biofeedback was initiated. The protocol provided for 10 weekly sessions of 15 minutes' duration with additional reinforcement sessions at 1, 3, 6, and 12 months. Subjective symptoms related to urgency, frequency, nocturia, and number of pad changes were reported by patients before treatment and at each visit. Digital evaluation of the pelvic floor muscle contraction was objectively graded from 0 to 3 (nil to strong) and was completed before and after treatment. These subjective and objective findings were used to determine success of treatment. RESULTS: Of the 27 patients completing the full treatment course, 13 (48%) had complete success, 7 (26%) had significant improvement but were not completely dry, and 7 (26%) had failure, for a total improvement rate of 74%. CONCLUSIONS: A biofeedback training program is an effective, minimally invasive, and well-accepted method that can be offered as a first-line option to patients who have undergone radical prostatectomy and want to improve the postsurgical problem of urinary incontinence. Patient motivation is an important factor in success. Nurses have an opportunity to use their expertise in this program to assist these patients to return to continence.
PURPOSE/OBJECTIVES: To examine oncology nurses' perceptions of their professional image and describe implications and strategies for practice. DATA SOURCES: Individuals in 28 Oncology Nursing Society (ONS) image focus groups and 13 validation focus groups in local ONS chapters throughout the United States. DATA SYNTHESIS: Although they used both negative and positive descriptors, participants believed the primary perceptions of physicians, administrators, and other nurses regarding oncology nurses were negative, whereas the perceptions of patients and families generally were more positive. Participants believed a lack of understanding exists about oncology nurses, their duties, and the impact of their specialized skills and knowledge on patient-care outcomes. They also believed that the current image of oncology nursing was not one they desired. CONCLUSIONS: Oncology nurses were concerned about their image and believed their external publics (e.g., physicians, administrators, nononcology nurses, patients, families) did not have a clear picture of who they are and what they do. They felt this lack of understanding led to diminished relationships with colleagues and patients/families and a lack of recognition of the oncology nurse as a valued member of the healthcare team. Participants felt this image could be changed and identified strategies to achieve their desired image through activities related to research, education, professionalism, communication, and influence. IMPLICATIONS FOR NURSING PRACTICE: Understanding the possible barriers to collaborative relationships, cost-effective care, disparate feelings of colleagues and external publics, and negative stereotypes will foster strategies to enhance relationships and improve care.
Increasing phosphorylation reactions by protein kinase A (PKA) or reducing dephosphorylation reactions of protein phosphatase-2A (PP-2A) increases the invasiveness of Lewis lung carcinoma (LLC) cells, as measured by their capacity to traverse extracellular matrix (ECM)-coated filters. Metastatic LLC-LN7 variants have reduced PP-2A activity when compared to nonmetastatic LLC-C8 variants. Immunoblotting showed that this reduced level of PP-2A activity was not due to reduced levels of the PP-2A catalytic (C) subunit. The cellular PP-2A activity could be stimulated by addition of C2-ceramide to LLC-LN7 lysates, or by incubating cells with either C2-ceramide or with a noncalcemic analog of vitamin D3, which has previously been shown to stimulate the release of ceramide. These treatments to elevate PP-2A activity in metastatic LLC-LN7 cells resulted in a decline in their capacity to invade through select (ECM) components, particularly through vitronectin and laminin. Underscoring the importance of PP-2A in limiting the invasiveness of tumor cells was the demonstration that LLC-LN7 cell transfectants overexpressing the PP-2A C alpha subunit were less invasive through ECM components than the wild-type cells. Invasion by these cells was further reduced by additionally increasing PP-2A activity by incubation with C2-ceramide or the vitamin D3 analog. These results suggest a role of a vitamin D3/ceramide/PP-2A pathway in limiting the invasiveness of tumor cells through select ECM components.
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Chromosome analysis was performed on a 3-year-old boy because of bilateral radioulnar synostosis and demonstrated a mosaic karyotype 46,XY/47,XYY/48,XYYY. He had minor facial anomalies and mild intellectual delay. He appears to be the youngest patient reported with this rare chromosome complement. His father, mother, and brother had normal chromosomes. Fluorescence in situ hybridization (FISH) was performed on the propositus and his father with the Y chromosome heterochromatic probe (pHY3.4) to add to the evaluation of mosaicism.