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Biomedical subjects

J Flanagan

Publications and source records attributed to J Flanagan.

At least 55 records · Page 3Linked to original sources
PubMed1998

Parry-Romberg syndrome associated with intracranial vascular malformations.

We describe a 23-year-old woman with iridocyclitis, enophthalmos, facial hemiatrophy, and transient numbness of her contralateral upper and lower extremities. The patient was found to have white matter densities in the right hemisphere in magnetic resonance T2-weighted images and vascular malformations involving right vertebral, right carotid, and right anterior cerebral arteries. Histopathologic evaluation of a biopsy specimen of anterior orbital fat and lacrimal gland revealed fibrosis and chronic inflammation. These findings were consistent with the diagnosis of progressive facial hemiatrophy (Parry-Romberg syndrome) in association with iridocyclitis and intracranial vascular malformations.

Adipose Tissue↗
PubMed1998

Susceptibility of stromelysin 1-deficient mice to collagen-induced arthritis and cartilage destruction.

OBJECTIVE: It has long been proposed that stromelysin is one of the major degradative matrix metalloproteinases responsible for the loss of cartilage in rheumatoid arthritis (RA) and osteoarthritis (OA). This hypothesis was tested by examining the arthritic paws of stromelysin 1 (SLN1)-deficient mice for loss of cartilage and for generation of neoepitopes that would be indicative of aggrecan cleavage. METHODS: The SLN1 gene was inactivated in murine embryonic stem cells, and knockout mice deficient in SLN1 activity were bred onto the B10.RIII background. The incidence and severity of collagen-induced arthritis (CIA) were compared in wild-type and knockout mice. Paws from mice with CIA were examined for loss of cartilage and for proteoglycan staining, as well as for the generation of the neoepitope FVDIPEN341. RESULTS: SLN1-deficient mice developed CIA, as did the wild-type N2 mice. Histologic analyses demonstrated no significant differences among the B10.RIII, wild-type, and knockout mice in loss of articular cartilage and proteoglycan staining. No decrease in the FVDIPEN341 epitope was observed in the SLN1-deficient mice. CONCLUSION: Disruption of the SLN1 gene neither prevents nor reduces the cartilage destruction associated with CIA. Moreover, SLN1 depletion does not prevent the cleavage of the aggrecan Asn341-Phe342 bond.

Animals↗
PubMed1998

Characterization of the haemolytic activity of Streptococcus equi.

The haemolytic activity of Streptococcus equi, the cause of equine strangles, was characterized. Production of haemolysin in Todd Hewitt broth was dependent on an equine serum supplement and the logarithmic phase of growth after which activity declined sharply. RNA core also induced haemolysin production from cells harvested at the end of the logarithmic phase of growth. Haemolysis was not affected by cholesterol, was only slightly increased in reducing conditions and was completely inactivated by trypan blue, identifying the haemolytic activity as streptolysin S-like (SLS-like). Purification by hydroxyapatite and Sephacryl column chromatography yielded proteins of molecular weights of approximately 6000 and 17 000-22 000 Da with a 64-fold increase in specific activity. Low molecular weight proteins from the RNA core were still present in the purified toxin. Two non-haemolytic mutants were derived by conjugation with an Enterococcus faecalis-carrying transposon Tn916. Southern blots of HindIII digests of DNA revealed that one of the mutants contained three transposon insertions and the other just one. A lambda phage library of S. equi contained plaques whose haemolytic activity was enhanced by reducing conditions and inhibited by cholesterol, suggesting a streptolysin O-like (SLO-like) activity. However, haemolysin in culture sonicates of host E. coli in which the lambda phage insert was subcloned into plasmid (pUC18), was not affected by these conditions. Seven isolates of S. equi in medium without SLS-like inducers showed no SLO-like activity and no evidence for an SLO-like toxin could be found by immunoblotting with pneumolysin antiserum and monoclonal antibodies or by polymerase chain reaction with primers derived from sequences conserved between the SLO genes of Lancefield group A, C and G streptococci. S. equi does not appear to possess a streptolysin O but does make a streptolysin S-like toxin whose production can be interrupted at just one genetic locus.

Antibodies, Bacterial↗
PubMed1998

Achieving partnership: the contribution of nursing education to the production of a flexible workforce.

AIM: This paper examines education's contribution to labour force reform in the nursing profession within the United Kingdom. BACKGROUND: In a globalized society there is increasing demand for more flexible forms of working. Nursing faces radical change in its employment characteristics if it is to continue to meet the health care needs of the population in the new century. ORIGINS OF INFORMATION AND DATA ANALYSIS: Key sociological texts and contemporary analysis of nursing skill have been analysed and synthesized to identify the dynamic of change in nursing and nursing education's contribution to these changes. KEY ISSUES: Patterns of upskilling and multiskilling are leading to the breakdown of professional role boundaries in the broader workforce. These patterns can also be seen in nursing. Upskilling is associated with increased stress and 'risk' for the individual, therefore achievement of flexibility is not without cost. Changes in the skill level in nursing lead many to conclude that the profession will become divided into a core and periphery distinction. This simplistic analysis does not account for the complexities of nursing and nursing skill although there is clearly a growing need for a 'knowledge and technical elite'. CONCLUSIONS: The core-periphery distinction is too simplistic to analyse nursing skills and the dynamic of change in the workforce. A radical perspective of nursing characterized by workers with a range of skills and competencies is less likely to lead to rigid professional boundaries. There is a clear need for multiskilled and knowledgeable workers; the 'technical and knowledge elite'. These nurses may be recognized as advanced practice nurses. High quality education is required to prepare these practitioners. Adaptation of nursing to the postmodern world needs to be facilitated by changes in current educational policy and practice.

Clinical Competence↗
PubMed1998

Scanning laser tomography: effect of change in keratometry values on retinal distance measures.

Scanning laser tomography is an objective non-invasive method for the three-dimensional imaging of the eye in-vivo. It has become a valuable tool in the diagnosis and monitoring of changes to the fundus and optic nerve head in diseases such as glaucoma. Optical errors should be eliminated where possible to improve accuracy and maximise the potential for the detection of subtle change due to disease progression. Alterations in the keratometry reading cause scaling changes in the (x, y) plane. This study demonstrated the importance of the keratometry value on retinal measurements. Accurate fundus measurements require input of the appropriate keratometry value for each subject, while for the detection of subtle change over time in longitudinal study, the keratometry reading should not be altered from baseline.

Adult↗
PubMed1997

Aggrecan degradation in human cartilage. Evidence for both matrix metalloproteinase and aggrecanase activity in normal, osteoarthritic, and rheumatoid joints.

To examine the activity of matrix metalloproteinases (MMPs) and aggrecanase in control and diseased human articular cartilage, metabolic fragments of aggrecan were detected with monospecific antipeptide antibodies. The distribution and quantity of MMP-generated aggrecan G1 fragments terminating in VDIPEN341 were compared with the distribution of aggrecanase-generated G1 fragments terminating in NITEGE373. Both types of G1 fragments were isolated from osteoarthritic cartilage. The sizes were consistent with a single enzymatic cleavage in the interglobular domain region, with no further proteolytic processing of these fragments. Both neoepitopes were also detected by immunohistochemistry in articular cartilage from patients undergoing joint replacement for osteoarthritis (OA), rheumatoid arthritis (RA), and in cartilage from adults with no known joint disease. In control specimens, the staining intensity for both G1 fragments increased with age, with little staining in cartilage from 22-wk-old fetal samples. There was also an increase with age in the extracted amount of MMP-generated neoepitope in relation to both aggrecan and collagen content, confirming the immunohistochemical results. After the age of 20-30 yr this relationship remained at a steady state. The staining for the MMP-generated epitope was most marked in control cartilage exhibiting histological signs of damage, whereas intense staining for the aggrecanase-generated fragment was often noted in adult cartilage lacking overt histological damage. Intense staining for both neoepitopes appeared in the more severely fibrillated, superficial region of the tissue. Intense immunostaining for both VDIPEN- and NITEGE- neoepitopes was also detected in joint cartilage from patients with OA or RA. Cartilage in these specimens was significantly more degraded and high levels of staining for both epitopes was always seen in areas with extensive cartilage damage. The levels of extracted VDIPEN neoepitope relative to collagen or aggrecan in both OA and RA samples were similar to those seen in age-matched control specimens. Immunostaining for both types of aggrecan fragments was seen surrounding the cells but also further removed in the interterritorial matrix. In some regions of the tissue, both neoepitopes were found while in others only one was detected. Thus, generation and/or turnover of these specific catabolic aggrecan fragments is not necessarily coordinated. Our results are consistent with the presence in both normal and arthritic joint cartilage of proteolytic activity against aggrecan based on both classical MMPs and "aggrecanase."

Adolescent↗
PubMed1996

A zinc finger-like domain of the molecular chaperone DnaJ is involved in binding to denatured protein substrates.

The Escherichia coli heat-shock protein DnaJ cooperates with the Hsp70 homolog DnaK in protein folding in vitro and in vivo. Little is known about the structural features of DnaJ that mediate its interaction with DnaK and unfolded polypeptide. DnaJ contains at least four blocks of sequence representing potential functional domains which have been conserved throughout evolution. In order to understand the role of each of these regions, we have analyzed DnaJ fragments in reactions corresponding to known functions of the intact protein. Both the N-terminal 70 amino acid 'J-domain' and a 35 amino acid glycine-phenylalanine region following it are required for interactions with DnaK. However, only complete DnaJ can cooperate with DnaK and a third protein, GrpE, in refolding denatured firefly luciferase. As demonstrated by atomic absorption and extended X-ray absorption fine structure spectroscopy (EXAFS), the 90 amino acid cysteine-rich region of DnaJ contains two Zn atoms tetrahedrally coordinated to four cysteine residues, resembling their arrangement in the C4 Zn binding domains of certain DNA binding proteins. Interestingly, binding experiments and cross-linking studies indicate that this Zn finger-like domain is required for the DnaJ molecular chaperone to specifically recognize and bind to proteins in their denatured state.

Absorptiometry, Photon↗
PubMed1995

Research in speech communication.

Advances in digital speech processing are now supporting application and deployment of a variety of speech technologies for human/machine communication. In fact, new businesses are rapidly forming about these technologies. But these capabilities are of little use unless society can afford them. Happily, explosive advances in microelectronics over the past two decades have assured affordable access to this sophistication as well as to the underlying computing technology. The research challenges in speech processing remain in the traditionally identified areas of recognition, synthesis, and coding. These three areas have typically been addressed individually, often with significant isolation among the efforts. But they are all facets of the same fundamental issue--how to represent and quantify the information in the speech signal. This implies deeper understanding of the physics of speech production, the constraints that the conventions of language impose, and the mechanism for information processing in the auditory system. In ongoing research, therefore, we seek more accurate models of speech generation, better computational formulations of language, and realistic perceptual guides for speech processing--along with ways to coalesce the fundamental issues of recognition, synthesis, and coding. Successful solution will yield the long-sought dictation machine, high-quality synthesis from text, and the ultimate in low bit-rate transmission of speech. It will also open the door to language-translating telephony, where the synthetic foreign translation can be in the voice of the originating talker.

Communication↗
PubMed1995

rHox: a homeobox gene expressed in osteoblastic cells.

Homeodomain proteins are characterized by a conserved domain with a helix-turn-helix motif. These proteins act as regulatory factors in tissue differentiation and proliferation. However, their role in the regulation of osteoblast differentiation is unknown. In this study we have identified and characterized a homeobox gene in osteoblast-like cells. This gene, termed rHox, was isolated from a cDNA library derived from rat osteoblast-like cells. The nucleotide sequence of the 1,375 base pair (bp) cDNA contains a noncoding leader sequence of 329 bp, a 735 bp open reading frame, and 312 bp of 3' noncoding sequence. Sequence comparison demonstrates that rHox is identical to the mouse Pmx gene (also called MHox) at the amino acid level and 90% homologous at the nucleotide level. Both Southwestern blotting and gel shift analyses indicate that rHox has potential to bind both the collagen I alpha 1 and the osteocalcin promoters. Transfection experiments using an rHox expression vector showed a strong repression of target promoter activity, regardless of whether the target promoters contained homeodomain binding response elements. These data suggest that rHox is a potent negative regulator of gene expression, although the specific role of rHox in bone gene regulation remains to be determined.

3T3 Cells↗
PubMed1995

Vascular erosion caused by a double-lumen central venous catheter during therapeutic plasma exchange.

BACKGROUND: The use of large-bore double-lumen dialysis catheters has simplified the procedure of therapeutic plasma exchange, but these catheters are associated with unusual and possibly life-threatening complications. CASE REPORT: A 46-year-old black man was admitted to the hospital with acute onset of paresthesia and weakness. A diagnosis of Guillain-Barré syndrome was made. Plasma exchange therapy was instituted by peripheral venous access. After three such exchanges, a double-lumen central venous catheter was placed via the left subclavian vein on hospital Day 7. The patient experienced a sudden onset of severe chest pain and dyspnea during the fourth plasma exchange. He became diaphoretic and hypotensive and experienced tachycardia. The apheresis procedure was stopped. Because of worsening respiratory distress, endotracheal intubation was performed. A chest x-ray revealed a large right pleural effusion. The central venous catheter was removed. A chest tube was placed, and a large amount of bloody fluid was drained. Several days later, the endotracheal and chest tubes were removed. CONCLUSION: An unusual complication of the use of a central venous catheter, erosion of the superior vena cava, occurred during therapeutic plasma exchange. Prompt recognition of this complication and appropriate therapy can be life-saving.

Blood Component Removal↗
PubMed1994

The ATP hydrolysis-dependent reaction cycle of the Escherichia coli Hsp70 system DnaK, DnaJ, and GrpE.

Molecular chaperones of the Hsp70 class bind unfolded polypeptide chains and are thought to be involved in the cellular folding pathway of many proteins. DnaK, the Hsp70 protein of Escherichia coli, is regulated by the chaperone protein DnaJ and the cofactor GrpE. To gain a biologically relevant understanding of the mechanism of Hsp70 action, we have analyzed a model reaction in which DnaK, DnaJ, and GrpE mediate the folding of denatured firefly luciferase. The binding and release of substrate protein for folding involves the following ATP hydrolysis-dependent cycle: (i) unfolded luciferase binds initially to DnaJ; (ii) upon interaction with luciferase-DnaJ, DnaK hydrolyzes its bound ATP, resulting in the formation of a stable luciferase-DnaK-DnaJ complex; (iii) GrpE releases ADP from DnaK; and (iv) ATP binding to DnaK triggers the release of substrate protein, thus completing the reaction cycle. A single cycle of binding and release leads to folding of only a fraction of luciferase molecules. Several rounds of ATP-dependent interaction with DnaK and DnaJ are required for fully efficient folding.

Adenosine Triphosphatases↗
PubMed1994

Waterloo Vision and Mobility Study: gait adaptations to altered surfaces in individuals with age-related maculopathy.

Walking is an extremely complex task that can become seriously challenged if one of the sensory systems which provides input to the motor system is compromised. The present study evaluated gait adaptations to altered surface characteristics and high and low ambient light conditions by subjects with age-related maculopathy (ARM). Twenty subjects with ARM and 20 control subjects walked along a 6 m path, along which they met 1 of 3 altered surfaces (compliant, uneven, or shiny). Kinematic data and ground reaction forces information were analyzed to discern gait adaptation strategies used by the ARM group. Ten trials on each surface were collected under both high and low ambient light levels. The ARM subjects were found to be generally more cautious when walking on the altered surfaces. For example, they walked more slowly, with a longer swing time. However, gait adaptations in the ARM group were not merely scaled versions of normal gait but were adjustments to adapt to environmental changes. Gait was modified to avoid tripping over a surface edge, to prevent slipping at heel contact, and to balance during stance. These adaptations enabled subjects to maintain safe mobility when walking in a challenging environment.

Adaptation, Physiological↗
PubMed1993

Thermal unfolding of staphylococcal nuclease and several mutant forms thereof studied by differential scanning calorimetry.

The effects of eight mutations on the thermodynamics of the reversible thermal unfolding of staphylococcal nuclease have been determined over a range of pH and protein concentration by means of differential scanning calorimetry. Variation of the protein concentration was included in our study because we found a significant dependence of the thermodynamics of protein unfolding on concentration. Values for the change in the standard free energy of unfolding, delta delta G0d, produced by the mutations in the pH range 5.0-7.0 varied from 1.9 kcal mol-1 (apparent stabilization) for H124L to -2.8 kcal mol-1 (apparent destabilization) for L25A. As has been observed in numerous other cases, there is no correlation in magnitude or sign between delta delta G0d and the corresponding values for delta delta Hd and T delta delta S0d, the latter quantities being in most cases much larger in magnitude than delta delta G0d. This fact emphasizes the difficulty in attempting to correlate the thermodynamic changes with structural changes observed by X-ray crystallography.

Calorimetry, Differential Scanning↗
PubMed1993

Relative sensitivity of clinical tests to hydrophilic lens-induced corneal thickness changes.

The relative sensitivity of the van den Berg Straylightmeter, slitlamp biomicroscopy, a modified optical pachometer, Bailey-Lovie logMAR visual acuity (VA), and two glare tests (The Brightness Acuity Tester used with 10% contrast VA and Pelli-Robson contrast sensitivity) to hydrophilic contact lens-induced edema was assessed in 19 subjects (mean age 25.9 +/- 4.5 years). After baseline assessments, subjects wore thick hydrogel lenses on one eye which was patched tightly for 3 h. Assessments were repeated at frequent intervals after lens removal to assess recovery. None of the pachometer measurements returned to baseline within the 2-h monitoring period, although the majority were within 2% of baseline corneal thickness. The average time for the Straylightmeter scores to recover to baseline values after the lens removal was 90 min, which was similar to the time when visible edema at the slitlamp disappeared. The average time for return to baseline of logMAR VA and the two glare tests was consistently two to three times shorter than the time for the Straylightmeter score. The Straylightmeter therefore provided assessments of corneal edema similar to slitlamp examination and was more sensitive than VA or glare testing.

Adult↗
PubMed1992

Successive action of DnaK, DnaJ and GroEL along the pathway of chaperone-mediated protein folding.

The main stress proteins of Escherichia coli function in an ordered protein-folding reaction. DnaK (heat-shock protein 70) recognizes the folding polypeptide as an extended chain and cooperates with DnaJ in stabilizing an intermediate conformational state lacking ordered tertiary structure. Dependent on GrpE and ATP hydrolysis, the protein is then transferred to GroEL (heat-shock protein 60) which acts catalytically in the production of the native state. This sequential mechanism of chaperone action may represent an important pathway for the folding of newly synthesized polypeptides.

Bacterial Proteins↗
PubMed1992

99mTechnetium-labelled red blood cell scintigraphy as an alternative to angiography in the investigation of gastrointestinal bleeding: clinical experience in a district general hospital.

99mTechnetium-labelled red blood cell scintigraphy (99mTc RBC scintigraphy) was used as the second-line investigation to localise bleeding in 23 patients (11 male, 12 female; mean age 67 years) presenting with active bleeding per rectum. Scintigraphy was available on a 24 h basis. A total of 18 patients had positive scans (78%). Surgery was performed urgently in 11 patients and the site of bleeding, as predicted by scintigraphy, was confirmed in 9 (82%). 99mTc RBC scintigraphy was less useful in patients who were not bleeding actively or who were being investigated for chronic anaemia. This study suggests that 99mTc RBC scintigraphy can play a useful role in the preoperative localisation of unexplained gastrointestinal bleeding in hospitals with nuclear medicine facilities, but confirms it has little place in the management of patients unless they are bleeding actively.

Adult↗
PubMed1991

The molecular basis of partitioning in aqueous two-phase systems.

Protein purification based on partition in aqueous two-phase systems has attracted interest for many years. This approach has been advocated as a primary-stage unit operation in downstream processing. In reality, application has been strictly limited through inadequate understanding of the complex molecular forces involved in partitioning processes.

Amino Acid Sequence↗