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Biomedical subjects

S Hagan

Publications and source records attributed to S Hagan.

At least 19 recordsLinked to original sources
PubMed2002

Quantum computation in brain microtubules: decoherence and biological feasibility.

The Penrose-Hameroff orchestrated objective reduction (orch. OR) model assigns a cognitive role to quantum computations in microtubules within the neurons of the brain. Despite an apparently "warm, wet, and noisy" intracellular milieu, the proposal suggests that microtubules avoid environmental decoherence long enough to reach threshold for "self-collapse" (objective reduction) by a quantum gravity mechanism put forth by Penrose. The model has been criticized as regards the issue of environmental decoherence, and a recent report by Tegmark finds that microtubules can maintain quantum coherence for only 10(-13) s, far too short to be neurophysiologically relevant. Here, we critically examine the decoherence mechanisms likely to dominate in a biological setting and find that (1) Tegmark's commentary is not aimed at an existing model in the literature but rather at a hybrid that replaces the superposed protein conformations of the orch. OR theory with a soliton in superposition along the microtubule; (2) recalculation after correcting for differences between the model on which Tegmark bases his calculations and the orch. OR model (superposition separation, charge vs dipole, dielectric constant) lengthens the decoherence time to 10(-5)-10(-4) s; (3) decoherence times on this order invalidate the assumptions of the derivation and determine the approximation regime considered by Tegmark to be inappropriate to the orch. OR superposition; (4) Tegmark's formulation yields decoherence times that increase with temperature contrary to well-established physical intuitions and the observed behavior of quantum coherent states; (5) incoherent metabolic energy supplied to the collective dynamics ordering water in the vicinity of microtubules at a rate exceeding that of decoherence can counter decoherence effects (in the same way that lasers avoid decoherence at room temperature); (6) microtubules are surrounded by a Debye layer of counterions, which can screen thermal fluctuations, and by an actin gel that might enhance the ordering of water in bundles of microtubules, further increasing the decoherence-free zone by an order of magnitude and, if the dependence on the distance between environmental ion and superposed state is accurately reflected in Tegmark's calculation, extending decoherence times by three orders of magnitude; (7) topological quantum computation in microtubules may be error correcting, resistant to decoherence; and (8) the decohering effect of radiative scatterers on microtubule quantum states is negligible. These considerations bring microtubule decoherence into a regime in which quantum gravity could interact with neurophysiology.

Actins↗
PubMed2002

Pathobiology of epiretinal and subretinal membranes: possible roles for the matricellular proteins thrombospondin 1 and osteonectin (SPARC).

Epiretinal and subretinal membranes are fibrocellular proliferations which form on the surfaces of the neuroretina as a sequel to a variety of ocular diseases. When these proliferations complicate rhegmatogenous retinal detachment (a condition known as proliferative vitreoretinopathy or PVR), the membranes often contain numerous retinal pigment epithelial (RPE) cells and a variety of extracellular proteins. The extracellular proteins include adhesive proteins like collagen, laminin and fibronectin. In addition, several matricellular proteins with potential counter-adhesive functions are present in the membranes. Two such matricellular proteins, thrombospondin 1 and osteonectin (or SPARC: Secreted Protein Acidic and Rich in Cysteine), tend to be co-distributed with the RPE cells in PVR membranes. By virtue of their counter-adhesive properties, thrombospondin 1 and SPARC may reduce RPE cell-matrix adhesion and so permit key RPE cellular activities (for example, migration or shape change) in periretinal membrane development. Furthermore, within a 'cocktail' containing other proteins such as the metalloproteinases and growth factors like the scatter factor/hepatocyte growth factor family, matricellular proteins may play a role in the RPE cell dissociation from Bruch's membrane, which characterises early PVR.

Epiretinal Membrane↗
PubMed2001

Overexpression of epidermal growth factor receptor restricted to macrophages in uveal melanoma.

OBJECTIVE: To determine whether expression of the epidermal growth factor receptor (EGFR) is of prognostic value in uveal melanoma. METHODS: Thirty consecutive patients treated for primary posterior uveal melanoma by enucleation or local resection were studied. Tumors were examined for EGFR and CD68 expression by immunohistochemistry on formalin-fixed, paraffin-embedded sections. Extracted DNA from paired frozen tumor and blood samples was examined for loss of heterozygosity on chromosome 3 using polymerase chain reaction-based microsatellite analysis. Immunoreactivity for EGFR was correlated with clinicopathological, chromosome 3, and follow-up data. RESULTS: Immunoreactivity for EGFR was observed in 7 (23%) of 30 uveal melanomas, but was restricted to solitary or small groups of cells with macrophage-like morphology. Immunoreactive cells were confirmed as macrophages using an antibody to the macrophage marker CD68. Chromosome 3 loss, epithelioid cells, and microvascular loops were detected in 17 (57%), 22 (73%) and 19 (63%) of the 30 tumors, respectively. Metastatic disease was detected in 5 patients (17%). No correlation was found between any of these variables and EGFR positivity. CONCLUSIONS: The absence of EGFR immunoreactivity in tumor cells does not support the use of EGFR expression as a prognostic indicator in patients with uveal melanoma. Future EGFR studies in uveal melanoma should be interpreted with caution in view of our findings that tumor-associated macrophages can express this receptor.

Antigens, CD↗
PubMed2001

Loss of heterozygosity on chromosomes 3, 9, 13, and 17, including the retinoblastoma locus, in uveal melanoma.

PURPOSE: To identify tumor-suppressor loci that may contribute to the pathogenesis of uveal melanoma. METHODS: Multiplex fluorescence microsatellite assays were performed on 27 uveal melanomas using markers at 3p25-p26, 3p14.2, 9p21-p23, 13q14, 13q12.3-q13, and 17p13, close to or within the von Hippel Lindau (VHL), fragile histidine triad (FHIT), p16/cyclin-dependent kinase inhibitor 2 (CDKN2A), retinoblastoma (RB1), breast cancer 2 (BRCA2), and p53 tumor suppressor loci, respectively. Further markers on chromosomes 3 and 9 were analyzed individually. RESULTS: Loss of heterozygosity (LOH) was identified in 63% of tumors, most frequently on chromosome 3 (52%), in association with epithelioid cells (P = 0.0002) and microvascular loops (P = 0.0008). In the majority of cases, LOH on chromosome 3 was detected at all informative markers. The second most common alteration was LOH at an RB1 intragenic marker (21% tumors), with retention of a more centromeric 13q marker (near BRCA2). The pattern of LOH on chromosome 9p was consistent with the involvement of a region telomeric to CDKN2A. LOH at TP53 was infrequent. CONCLUSIONS: In the majority of cases, chromosome 3 LOH involves an entire chromosome homologue, which hampers identification of the relevant suppressor loci. This LOH correlates with the presence of microvascular loops and epithelioid cells, two of the recognized histologic indicators of poor prognosis. Data for chromosomes 13 and 9 support a role for RB1 in the pathogenesis of uveal melanoma but also raise the possibility of the involvement of additional loci close to RB1 and CDKN2A.

Acid Anhydride Hydrolases↗
PubMed2000

The role of positively charged amino acids in ATP recognition by human P2X(1) receptors.

P2X receptors for ATP are a family of ligand-gated cation channels. There are 11 conserved positive charges in the extracellular loop of P2X receptors. We have generated point mutants of these conserved residues (either Lys --> Arg, Lys --> Ala, Arg --> Lys, or Arg --> Ala) in the human P2X(1) receptor to determine their contribution to the binding of negatively charged ATP. ATP evoked concentration-dependent (EC(50) approximately 0.8 microm) desensitizing responses at wild-type (WT) P2X(1) receptors expressed in Xenopus oocytes. Suramin produced a parallel rightward shift in the concentration response curve with an estimated pK(B) of 6.7. Substitution of amino acids at positions Lys-53, Lys-190, Lys-215, Lys-325, Arg-202, Arg-305, and Arg-314 either had no effect or only a small change in ATP potency, time course, and/or suramin sensitivity. Modest changes in ATP potency were observed for mutants at K70R and R292K/A (20- and 100-fold decrease, respectively). Mutations at residues K68A and K309A reduced the potency of ATP by >1400-fold and prolonged the time course of the P2X(1) receptor current but had no effect on suramin antagonism. Lys-68, Lys-70, Arg-292, and Lys-309 are close to the predicted transmembrane domains of the receptor and suggest that the ATP binding pocket may form close to the channel vestibule.

Adenosine Triphosphate↗
PubMed2000

Estuarine and habitat-related differences in growth rates of young-of-the-year winter flounder (Pseudopleuronectes americanus) and tautog (Tautoga onitis) in three northeastern US estuaries.

Instantaneous growth rates of young-of-the-year winter flounder Pseudopleuronectes americanus (Walbaum) (12.0-60.4 mm standard length, SL) and tautog Tautoga onitis (Linnaeus) (21.4-73.8 mm total length, TL) from three estuarine systems in New Jersey (Great Bay-Little Egg Harbor and Navesink River) and Connecticut (Hammonasset River) were used in an attempt to assess the relative quality of selected nominal habitats. A series of short-term field caging experiments were conducted during 1994 and 1995 in: macroalgae (primarily, Ulva lactuca), eelgrass (Zostera marina), unvegetated areas adjacent to macroalgae and eelgrass and tidal creeks in Spartina dominated marsh. Growth rates varied with habitat, estuary and year. Comparisons across nominal habitats within and among estuaries did not show any one habitat with consistently higher growth, and growth was relatively independent of whether a habitat was vegetated or adjacent to vegetation. The growth rates of winter flounder and tautog from the Hammonasset River were not different among habitats in either year of the study. In the Great Bay-Little Egg Harbor, both winter flounder and tautog had higher growth rates in macroalgae with growth in eelgrass varying significantly between years. Conversely, in the Navesink River both species had higher growth rates in eelgrass. Environmental changes associated with temperature and dissolved oxygen appeared to influence growth rates. Winter flounder growth rate and survival was depressed in tidal marsh creeks in the three estuaries and in vegetated macroalgae habitats in the Navesink River where dissolved oxygen levels were often very low (<2 mgl(-1)) for extended periods. In summary, the growth rates of the young-of-the-year of these two species varied temporally and were dependent on the interaction of both the specific estuary and habitat in which the experiments took place. Further, habitat quality, as defined by relative growth rate, was difficult to evaluate because it can be variable and nominal habitat designations are often not sufficient to define the boundaries of a species habitat requirements.

Journal Article↗
PubMed2000

Hepatocyte growth factor/scatter factor in the eye.

Hepatocyte growth factor, also known as scatter factor (HGF/SF) is a multipotential cytokine which can produce a range of responses in target cells and its influence in the eye in health and disease is just beginning to be appreciated. Usually HGF/SF is synthesised by mesenchymally derived cells and targets and signals epithelial cells in a paracrine manner via their c-Met surface receptor. However, there is growing evidence for the existence of autocrine loops in a number of cell systems prominent among which are ocular cells such as the corneal endothelium, the lens epithelium, the retinal pigment epithelium (RPE) and others. Marked cellular proliferation is stimulated when activated HGF/SF is exposed to hepatocytes, renal epithelium, melanocytes and vascular endothelial cells but it is often a poor mitogen for other cell types. In target cells the cytokine promotes other bioactions such as junctional breakdown, shape change, cell scattering, directional and nondirectional migration, cell survival, invasive behaviour and/or tubule formation. These activities seem to depend on HGF/SF linking with the c-Met receptor and pathways to stimulate the various types of cytokine/receptor response are being unravelled at the present time. In corneal wound healing, HGF/SF is produced by stromal keratocytes and targets the repairing epithelium. HGF/SF is a constituent of tears, aqueous humour and vitreous humour at levels above that found in plasma although it is not clear how much is activated. Aqueous HGF/SF may well influence lens epithelial, corneal endothelial and trabecular meshwork cell survival. Vitreous levels of HGF/SF are elevated in proliferative vitreoretinopathy (PVR), where a target cell is the RPE and in proliferative diabetic retinopathy (PDR) where HGF/SF has been shown to be a major angiogenesis factor. Finally HGF/SF may be involved in the metastatic spread of tumour cells from uveal melanomata and in the formation of vascular channels in these tumours.

Animals↗
PubMed2000

Management of pain and pain-related symptoms in hospitalized veterans with cancer.

Unrelieved pain continues to be a problem among hospitalized patients with cancer. The purpose of this study was to evaluate pain management outcomes in a group of veterans with cancer receiving inpatient care. The sample consisted of 90 veterans with cancer hospitalized in one of two large veterans medical centers in the southeastern United States. Daily pain was assessed by administering the visual analog scale (VAS) for pain three times in a 24-hour period and averaging these three scores. The Brief Pain Inventory (BPI) and Constipation Assessment Scale (CAS) were administered once. The charts were audited using the Chart Audit for Pain (CAP). The sample was predominantly male (93.3%) and white (82.8%). The length of time since diagnosis ranged from newly diagnosed during this hospitalization to 16 years. Average daily pain was 32.9 on the VAS and 4 on the BPI. However, approximately one-fourth of the patients reported average daily pain above the midpoint (VAS > 50), and some patients reported average daily pain to be as high as 98. Fewer than half of charts (42%) showed evidence that a pain rating scale was used. Other assessment data also were very limited. Patients reported that pain interfered with all activities on the BPI, with highest interference scores for walking and sleep (mean, 5.5). Although 80% of the patients reported some problem with constipation, the chart audit indicated that this was recorded in only 11 patient records. No patient records indicated a problem with sedation. The findings indicate that limited attempts were made to manage pain using nonpharmacologic methods. In addition, only one of the nine charts reporting these attempts showed evidence that results from the attempt were evaluated. It may be concluded that pain management continues to be less than ideal in these veterans hospitals. Study results indicate that nurses are not documenting careful assessment of pain, not documenting evaluation of approaches to pain management, and not attending to the constipation that is inevitable when opioids are administered. Continued emphasis on nursing education related to pain management is needed. Future research should be undertaken to evaluate these outcomes.

Adult↗
PubMed2000

Synthesis of osteonectin by human retinal pigment epithelial cells is modulated by cell density.

PURPOSE: To determine whether human retinal pigment epithelial (HRPE) cells are able to synthesize the antiadhesive protein osteonectin, also known as secreted protein, acidic and rich in cysteine (SPARC). Additionally, because locally produced SPARC may modulate cellular behavior during tissue repair, to ascertain whether HRPE SPARC production and HRPE proliferation, migration, and/or differentiation are associated, in a simple HRPE wound-healing model. METHODS: Immunohistochemical and Western blot analyses of SPARC protein expression by low- and high-density cultured HRPE cells were undertaken. Total RNA extracted from cultures was studied by reverse transcription-polymerase chain reaction (RT-PCR) and Northern blot analysis. Western and Northern blot analyses were evaluated by densitometry. Experiments were repeated with HRPE cells cultured in the presence of 1, 10, or 100 microM of the differentiating agents butyric acid (BA) and retinoic acid (RA). RESULTS: HRPE cell cultures exhibited SPARC immunoreactivity. Western blot analysis of cell lysates and conditioned media showed a 43-kDa protein. RT-PCR and Northern blot analysis confirmed the presence of SPARC mRNA (with transcripts at 2.2 and 3.0 kb). Protein and mRNA transcript band densitometry revealed a higher proportion of SPARC protein and mRNA in high-density HRPE cell culture than in low-density culture. Neither BA nor RA (at the concentrations assessed) had a significant effect on SPARC production by HRPE cells in high- or low-density culture. CONCLUSIONS: HRPE can synthesize SPARC. Although the findings do not support an invariable association between SPARC production by HRPE and HRPE proliferation, migration, or differentiation, they demonstrate that synthesis of SPARC by HRPE is modulated by cell density.

Blotting, Northern↗
PubMed2000

Knowledge and attitudes of nurses in veterans hospitals about pain management in patients with cancer.

PURPOSE/OBJECTIVES: To assess nurses' knowledge and attitudes about pain management and patients in pain. DESIGN: Exploratory, descriptive. SETTING: Seven medical-surgical inpatient units in two large veterans hospitals in Southwest Florida. SAMPLE: A convenience self-select sample of 85 nurses (RNs and LPNs working on the target units on all shifts). METHODS: Staff nurses were approached at work and asked to complete the data collection forms. MAIN RESEARCH VARIABLES: Knowledge about pain management principles and attitudes toward pain management and patients in pain. FINDINGS: Areas of major knowledge deficits included physiology of pain and pharmacology of analgesics. Nurses were most knowledgeable about the importance of asking patients about their pain, around-the-clock scheduling, tolerance, and use of distraction. Patient behavior, age, and gender seemed to unduly influence nurses in their pain management decisions. Regarding attitudes about pain management, the majority of nurses did not agree that patients and their families should have the most control over analgesic scheduling and that a constant level of analgesic should be maintained in the blood. In fact, 82% indicated that around-the-clock analgesics increase the risk for sedation and respiratory depression. CONCLUSIONS: Years after the Agency for Health Care Policy and Research published pain guidelines, nurses in veterans hospitals continue to lack knowledge and have negative attitudes that may negatively affect pain management in patients with cancer. IMPLICATIONS FOR NURSING PRACTICE: Basic and continuing education for nurses needs to include intensive content about pain management. Continued research is needed to document improvements in pain management by nurses.

Adult↗
PubMed1997

Evanescent (tunneling) photon and cellular "vision'.

The existence of a rudimentary form of cellular 'vision' was discovered experimentally by Albrecht-Buehler. He found that Swiss 3T3 cells approached distant infrared light spots and suggested that the most likely explanation for this phenomenon involves the long-range processing of electromagnetic signals by the cells. In this paper, a theoretical possibility of this phenomenon is presented within the fully quantum theoretical framework of the electromagnetic field and water. By taking into account the usually neglected interaction between the electric dipole field of water molecules and the quantized electromagnetic field, the dynamically ordered region of water surrounding the cell up to the coherence length < 50 microns is shown to play the role of a nonlinear coherent optical device through which the cells receive electromagnetic signals from distant light spots. The electromagnetic signals for the cell Albrecht-Buehler found are shown to consist of evanescent photons (i.e. soft polaritons) tunneling through the dynamically ordered region of water between the cell and the distant light spot. In contrast to the (normal) vision of animals realized by receiving (normal) photons, cellular "vision' is found to be realized by receiving evanescent photons. It is also suggested that the existence of the dynamically ordered region of water realizing a boson condensation of evanescent photons inside and outside the cell can be regarded as the definition of life.

3T3 Cells↗
PubMed1997

Experience of clinical use of the Odstock dropped foot stimulator.

The Odstock dropped foot stimulator (ODFS) is a simple functional electrical stimulation (FES) device for the correction of dropped foot. Improved reliability, fine control of stimulation parameters, and careful application and follow-up have let to 86% compliance. Data on 56 patients (50 patients with hemiplegia, 5 patients with multiple sclerosis, and 1 patient with spinal cord injury) who have used the system for between 6 and 18 months are presented and show a statistically significant increase in walking speed with the stimulator at 3 months of 14% (p < 0.001); decreased effort of walking, measured as physiological cost index (PCI), of 37% (p < 0.001); and statistically significant improvement in functional mobility tests and questionnaires. No statistically significant carryover was seen although 3 patients had sufficient improvement in active ankle control and gait parameters to no longer need the stimulator. Six patients who used the stimulator all day every day had a problem with skin irritation, which we have not yet been able to solve. Two patients discontinued use after experiencing increased spasticity in the calf.

Electric Stimulation Therapy↗
PubMed1996

Directional-tip endotracheal tubes for blind nasotracheal intubation.

OBJECTIVES: To compare initial success rates of blind nasotracheal intubation using directional-tip endotracheal tubes vs standard endotracheal tubes. METHODS: A prospective trial comparing directional-tip and standard endotracheal tubes during initial attempts at blind nasotracheal intubation (BNTI) at a university hospital ED. Using an alternating schedule, the directional-tip or standard tube was used for the first attempt at BNT1. An attempt was defined as beginning when the tube was placed through the nose into the posterior pharynx and ending when the patient was intubated or the tube was removed from the nares. After the intubation, the physician graded the difficulty of the technique (i.e., easy/routine, intermediate, difficult, or unable to intubate nasally). RESULTS: There were 49 patients entered over 5 months. Patient presentations for the intubations were trauma (45.8%), overdose (33.3%), respiratory/cardiac event (12.5%), seizure (2.1%), and other (6.3%). Intubation was successful on the first attempt in 18 of 21 patients (86%; 95% CI, 64% to 97%) for the directional-tip tube vs 16 of 28 patients (57%; 95% CI, 37% to 76%) for the standard tube (p = 0.03). The groups did not differ in age, sex, clinical presentation, or perceived difficulty of intubation. Only 1 patient could not be intubated nasally and was subsequently intubated orally. CONCLUSION: The use of directional-tip tubes may improve the success rate of the first attempt at BNTI.

Adolescent↗