PubMed Health⌕ Search

Biomedical subjects

L Vaughan

Publications and source records attributed to L Vaughan.

At least 37 records · Page 2Linked to original sources
PubMed1997

Comparison of train-of-four and best clinical assessment during continuous paralysis.

Train-of-four (TOF) monitoring is recommended in published guidelines during use of continuous-infusion neuromuscular blocking agents (NMB) in the intensive care unit (ICU). To test that recommendation, dual protocols were established in a medical ICU after intensive nursing education. Paralyzed patients received either TOF monitoring with a goal of three twitches or best clinical assessment while receiving atracurium by continuous infusion. Demographics and mean duration of paralysis of 20 patients in the TOF group were no different than that of the 16 patients in the best clinical assessment group. Although most patients demonstrated atracurium tolerance over time, there was no difference between groups in total mg (+/- SEM) infused (10,460 +/- 2,409 versus 9,201 +/- 3,237) or mean microgram/kg/min (15.2 +/- 1.5 versus 12.0 +/- 1.1). The time to clinical recovery was no different between groups (50 +/- 10 versus 45 +/- 12 min). Two complications occurred in the TOF group, with pulmonary emboli despite prophylaxis and an unrecognized cerebrovascular accident in one patient each. We conclude that careful titration of NMB using clinical bedside markers should remain the standard of care with these drugs.

Adult↗
PubMed1996

Binding of contactin/F11 to the fibronectin type III domains 5 and 6 of tenascin is inhibited by heparin.

The structural basis for the interaction between tenascin-C and the neuronal cell adhesion molecule, contactin/F11, was investigated using plasmon surface resonance technology. The binding site on tenascin-C for contactin/F11 is shown to span the two fibronectin type III homology domains 5 and 6. Either domain alone is insufficient for binding. Heparin, heparan sulfate and dermatan sulfate inhibit this interaction through binding to a conserved heparin-binding site on domain 5. In contrast, chondroitin sulfates A and C have no such effect.

Animals↗
PubMed1996

Intraosseous ganglion of the patella.

Osteolytic cystic lesions of the patella are rare lesions. A review of the literature revealed only one previously reported example. The pathogenesis and radiological and pathological features of intraosseous ganglion cysts are discussed. In addition, the differential diagnosis of lytic patellar lesions is discussed.

Aged↗
PubMed1996

Clear-cell chondrosarcoma with elevated alkaline phosphatase, mistaken for osteosarcoma on biopsy.

This paper report a case of a pelvic clear-cell chondrosarcoma that was initially diagnosed as clear-cell osteosarcoma after needle biopsy. Preoperatively, laboratory studies revealed an elevated alkaline phosphatase and needle biopsy showed clear cells producing osteoid. Internal hemipelvectomy was performed and final pathology was most consistent with clear-cell chondrosarcoma, despite a negative S-100 immunohistochemical stain. Distinguishing between these two entities is clinically important because treatment differs. In this case, the patient did not receive pre-or postoperative chemotherapy and is disease free more than 2 years later.

Acetabulum↗
PubMed1995

Tenascin-C binds heparin by its fibronectin type III domain five.

Two sites on tenascin mediate interactions with glycosaminoglycan chains of proteoglycans. One is situated on the fibrinogen-like domain, whereas the other lies within the fibronectin type III homology region (Aukhil, I., Joshi, P., Yan, Y.Z., and Erickson, H.P. (1993) J. Biol. Chem. 268, 2542-2553.). We now characterize the latter binding site more closely by means of recombinant protein fragments derived from the type III homology region of tenascin. Using a heparin-Sepharose column, we localize the second heparin binding site to the fifth fibronectin type III domain. This is confirmed in solid phase assays by incubation of fusion proteins with biotin-labeled heparin. In addition, we demonstrate the binding of heparan sulfate and dermatan sulfate to domain five. Molecular modelling of this domain reveals a conserved heparin-binding motif that we propose as the putative binding site. The fact, that different glycosaminoglycans may bind to this domain, implies that different classes of proteoglycans may in vivo compete for the same site.

Amino Acid Sequence↗
PubMed1995

The clinical course of treated and untreated Gaucher disease. A study of 45 patients.

One hundred nineteen patients with Gaucher disease were examined in the past 13 years. Of these 45 were examined 3 or more times over a time-span exceeding one year and all such patients are included in this study. Adult patients showed little progression of disease. There were few alterations in the blood counts, no increase in size of liver and spleen, and changes in skeletal lesions were largely confined to pre-existing lesions. Some children appeared to have more progressive disease, but since many of the children in this study were treated with alglucerase, it is difficult to draw conclusions about the natural progression of the disease at earlier ages. Treatment with alglucerase resulted in gradual normalization of blood counts, decrease in the size of liver and spleen, and parallel decreases in the serum angiotensin converting enzyme and chitotriosidase levels. Skeletal symptoms were decreased in all patients, and skeletal lesions showed modest improvement in patients treated for two years or more. The response of patients to low dose/high frequency (2.3 U/Kg 3 x weekly; 30 U/Kg/Mo) therapy was indistinguishable from the response observed and previously reported by others with much larger doses. Changing the dosage from 30 U/Kg/Mo to 120 U/Kg/Mo was not attended by any significant changes in response. Criteria for the selection of patients for treatment with alglucerase are proposed. We suggest that a starting dose of 15 to 30 U/Kg/month, fractionated 3 times weekly be used for all patients, regardless of severity or site of involvement, and that upward dosage adjustments be made only in such rare patients who may not respond adequately to this dose in 6 to 12 months.

Adolescent↗
PubMed1995

The glypiated neuronal cell adhesion molecule contactin/F11 complexes with src-family protein tyrosine kinase Fyn.

Glycosyl phosphatidylinositol-anchored glycoproteins of the immunoglobulin superfamily play an important role in the formation of neuronal networks during development. The mechanism whereby neuronal GPI-linked molecules transduce recognition signals remains to be established. Analysis of detergent-resistant immune-complexes reveals that the glypiated neuronal cell adhesion molecule contactin/F11 specifically complexes with the cytoplasmic, nonreceptor type src-family tyrosine kinase Fyn. Antibody-mediated cross-linking of contactin/F11 on embryonic chick neuronal cells leads to an increase of the Fyn-activity coprecipitated with contactin/F11, and elevates phosphorylation of an additional 75/80 K component within the contactin/F11-immune-complex. Additionally, binding of ligands, i.e., contactin/F11-specific antibody or tenascin-R, a natural ligand of contactin/F11, to the surface of HeLa transfectants expressing contactin/F11, causes capping of contactin/F11 and a concomitant change in the distribution of the intracellular kinase Fyn, thus confirming their physical association. This indicates that contactin/F11-mediated signaling requires Fyn.

Animals↗
PubMed1995

Photosensitization of murine tumor, vasculature and skin by 5-aminolevulinic acid-induced porphyrin.

The effects of topical and systemic administration of 5-aminolevulinic acid (ALA) were examined in several murine tumor systems with regard to porphyrin accumulation kinetics in tumor, skin and blood, vascular and tumor cell photosensitization and tumor response after light exposure. Marked, transient increases in porphyrin levels were observed in tumor and skin after systemic and topical ALA. Rapid, transient, dose-dependent porphyrin increases were also observed in blood; these were pronounced after systemic ALA injection and mild after topical application. They were highest within 1 h after ALA injection, thereafter declining rapidly. This matched the clearing kinetics of injected exogenous protoporphyrin IX (PpIX). Initially, vascular photosensitivity changed inversely to blood porphyrin levels, increasing gradually up to 5 h post-ALA, as porphyrin was clearing from the bloodstream. This pattern was again matched by injected, exogenous PpIX. After therapeutic tumor treatment vascular disruption of the tumor bed, while observed, was incomplete, especially at the tumor base. Minimal direct tumor cell kill was found at low photodynamic therapy (PDT) doses (250 mg/kg ALA, 135 J/cm2 light). Significant, but limited (< 1 log) direct photodynamic tumor cell kill was obtained when the PDT dose was raised to 500 mg/kg systemic ALA, followed 3 h later by 270 J/cm2, a dose that was however toxic to the animals. The further reduction of clonogenic tumor cells over 24 h following treatment was moderate and probably limited by the incomplete disruption of the vasculature. Tumor responses were highest when light treatment was carried out at the time of highest tumor porphyrin content rather than at the time of highest vascular photosensitivity. Tumor destruction did not reach the tumor base, regardless of treatment conditions.

Administration, Topical↗
PubMed1995

Versican is selectively expressed in embryonic tissues that act as barriers to neural crest cell migration and axon outgrowth.

Chondroitin sulfate proteoglycans have been implicated in the regulation of cell migration and pattern formation in the developing peripheral nervous system. To identify whether the large aggregating proteoglycan versican might be mediating these processes, we prepared monospecific antibodies against a recombinant core protein fragment of chick versican. The purified antibodies recognize the predominant versican splice-variants V0 and V1. Using these antibodies, we revealed a close correlation between the spacio-temporal expression of versican and the formation of molecular boundaries flanking or transiently blocking the migration pathways of neural crest cells or motor and sensory axons. Versican is present in the caudal sclerotome, the early dorsolateral tissue underneath the ectoderm, the pelvic girdle precursor and to a certain extent in the perinotochordal mesenchyme. Versican is completely absent from tissues invaded by neural crest cells and extending axons. Upon completion of neural crest cell migration and axon outgrowth, versican expression is shifted to pre-chondrogenic areas. Since versican inhibits cellular interactions with fibronectin, laminin and collagen I in vitro, the selective expression of versican within barrier tissues may be linked to a functional role of versican in the guidance of migratory neural crest cells and outgrowing axons.

Animals↗
PubMed1995

Immunization of prepubertal beef heifers against gonadotropin-releasing hormone: immune, estrus, ovarian, and growth responses.

To develop an effective immunization protocol against human serum albumin-Cys-Gly-GnRH (HSA-GnRH) conjugate to delay the onset of puberty in heifers, 58 heifers (8 mo of age; mean +/- SE BW = 203 +/- 1 kg) were randomly assigned to each of six treatments: 1) controls, .1 mg of HSA, with diethylaminoethyl (DEAE)-dextran as adjuvant, on d 0 and 28; 2) .1 mg of HSA-GnRH, with DEAE-dextran, on d 0; 3) as 2) and booster on d 28; 4) as 3) but boosters also on d 84, 140, 196, and 252; 5) as 2) but half the conjugate given with DEAE-dextran adjuvant and half with non-ulcerative Freund's adjuvant (NUFA), injected in two separate sites; and 6) as 2) but the conjugate given with DEAE-dextran and NUFA, emulsified and injected in two sites. The duration of the experiment was 342 d. Mean plasma GnRH antibody titers (samples every 2 wk) for heifers in Treatments 2 to 6 were 9.4 +/- 1.16, 20.6 +/- 2.21, 43.9 +/- 2.86, 27.9 +/- 2.67, and 44.5 +/- 3.75% binding at a plasma dilution of 1:640. The mean number of times estrus was observed in heifers was less (P < .05; pooled SEM = .53) in Treatments 4 (.2) and 6 (2.4) than in Treatments 1, 2, 3, and 5 (7.8, 7.0, 7.0, and 6.6, respectively). The mean interval to the onset of puberty (the first increase in plasma progesterone > or = .5 ng/mL for > or = 10 d with samples at 3- to 4-d intervals) was greater (P < .05; pooled SEM = 11.6) for heifers in treatments 4 (339 d) and 6 (276 d) than for heifers in Treatments 1, 2, 3, and 5 (164, 159, 165, and 170 d, respectively). Mean ADG of heifers was reduced (P < .05) in treatments 2, 3, 4, and 6 (.71, .72, .68, and .69 kg, respectively) compared with controls (.77). In summary, the multiple booster immunization treatment induced and maintained sufficient anti-GnRH titer to delay puberty for 175 d; a single immunization against GnRH with DEAE and NUFA increased antibody titers enough to delay puberty for 112 d. However, GnRH immunization treatments reduced ADG of heifers in Treatments 2, 3, 4, and 6.

Aging↗
PubMed1995

Contactin/F11 and tenascin-C co-expression in the chick retina correlates with formation of the synaptic plexiform layers.

The neural immunoglobulin-like cell adhesion molecule contactin/F11 and the extracellular matrix glycoprotein tenascin-C are prominent molecules in the developing nervous system which interact in in vitro assays (Zisch et al., J. Cell Biol. 119, 203-213). To determine their potential role in neural development, the distribution of tenascin-C and contactin/F11 was examined in the developing chick retina. The onset of both tenascin-C and contactin/F11 expression coincides with the appearance of ganglion cell dendrides and neurites from bipolar and amacrine cells in the inner layer (IPL) at E8, and the extension of bipolar and horizontal cell processes in the outer plexiform layer (OPL) at E9. Contactin/F11 expression is co-ordinately upregulated with the TN190 and TN200 tenascin-C isoforms between embryonic day 8 (E8) and E17, while little, if any, of the TN220 isoform, which does not bind contactin/F11, is detected. In situ hybridization reveals that tenascin-C and contactin/F11 mRNAs are synthesized by different neuronal types. Tenascin-C mRNA probes hybridize to amacrine and displaced amacrine neurons, and horizontal neurons. In cultured retinal cells, tenascin-C is also present on process-bearing neurofilament-positive cells. Contactin/F11 mRNA is detected in bipolar cells or their precursors from E8-9, and later in horizontal and ganglion neurons. The highest levels and greatest overlap in the synaptic IPL and OPL are reached at E17, when the stratification of the retina is nearly complete. These results are consistent with a putative role for contactin/F11-tenascin-C interactions in the establishment of synaptic layers in the retina.

Animals↗
PubMed1994

Tenascin-contactin/F11 interactions: a clue for a developmental role?

To understand how the extracellular matrix glycoprotein tenascin modifies cell adhesion and neurite outgrowth, we sought to isolate cellular receptors for tenascin. So far, two completely different cell surface ligands for tenascin have been detected. This we achieved by affinity chromatography of tissue extracts and of isolated proteins over tenascin-Sepharose and by solid-phase assays using the individual proteins. The first receptor, the neuronal cell adhesion molecule contactin/F11, a member of the immunoglobulin superfamily, binds to tenascin via a site in the N-terminal immunoglobulin-like domains. The binding site is within the fibronectin type III homology region at the boundary of the alternatively spliced region of tenascin, requiring that fibronectin type III homology domains 5 and 9 be adjacent, as they are in the 190 kD tenascin isoform. The close similarity in tertiary structure between type III domains and immunoglobulin-like repeats raises the possibility that we are observing a side-by-side interaction between the two molecules in a manner closely analogous to that between paired immunoglobulin domains. The second receptor is the heparan sulfate proteoglycan, glypican, which, similarly to contactin/F11, is anchored to the membrane via glycosylphosphatidylinositol. Glypican bound to a column of tenascin-Sepharose cannot be dissociated by chondroitin sulfate or dermatan sulfate, but elutes in a broad peak with a gradient of heparan sulfate and in a sharper peak with heparin. By means of fusion proteins, we have identified a potential binding site on the fifth fibronectin type III homology domain of tenascin. We are trying to define these sites more closely by means of site-directed mutagenesis. It will be interesting to see whether the interaction between tenascin and cell surface contactin/F11, and possibly cellular heparan sulfate proteoglycans, contributes to the prominent role played by tenascin in pattern formation during development of the nervous system. In a first step, we have examined the distribution of tenascin isoforms and contactin/F11 during retinal development by means of immunohistochemistry and in situ hybridization with tenascin isoform-specific probes. Tenascin isoforms 190/200 along with contactin/F11 are particularly prominent in the inner and outer plexiform layers of embryonic day 8 retina in the chick. This coordinate up-regulation was confirmed both by immunoblots and Northern blots of retinal extracts. A speculative model is presented to suggest how the unique hexabrachion may signal the cell via contactin/F11.

Amino Acid Sequence↗
PubMed1993

Lipid-associated methylpheophorbide-a (hexyl-ether) as a photodynamic agent in tumor-bearing mice.

Liposomes are a potential system for more selective delivery of photosensitizers (PS) to tumors. Pheophorbides are one series of new PS under investigation for use in photodynamic therapy. The pharmacokinetics, anti-tumor response and normal tissue effects of methylpheophorbide-a-(hexyl-ether) (MPH) associated with negatively charged phospholipid vesicles composed of high and low transition temperature lipids were determined in mice. In some preparations monosialoganglioside, which is known to impart long circulation time to liposomes was also included. Normally water-insoluble MPH could be quantitatively incorporated in multilamellar liposomes up to at least 20 mol MPH/mol lipid% for most liposome compositions and sonicated to form clear suspensions. Evidence from electron microscopy and entrapment of aqueous space markers indicated that the particles formed by sonication were not standard liposomes. Anti-tumor responses to light treatment (135 J/cm2, 665 nm argon-dye laser) 24 h after MPH (0.4 mumol/kg) administration were slightly but significantly greater (P < 0.05) for lipid associated MPH compared to MPH solubilized in Tween 80. There were no major differences in tumor uptake and tumor cell photosensitization between lipid or Tween 80 formulations of MPH, whereas, dependent on lipid composition and time after MPH administration, the doses of light required to cause occlusive vascular damage were increased for the lipid formulations. Pharmacokinetic studies showed rapid dissociation between lipids and MPH in vivo. Lipid formulations are useful for solubilizing MPH and may improve the therapeutic effects of this PS.

Animals↗
PubMed1992

Neuronal cell adhesion molecule contactin/F11 binds to tenascin via its immunoglobulin-like domains.

Adhesive interactions between neurons and extracellular matrix (ECM) play a key role in neuronal pattern formation. The prominent role played by the extracellular matrix protein tenascin/cytotactin in the development of the nervous system, tied to its abundance, led us to speculate that brain may contain yet unidentified tenascin receptors. Here we show that the neuronal cell adhesion molecule contactin/F11, a member of the immunoglobulin(Ig)-superfamily, is a cell surface ligand for tenascin in the nervous system. Through affinity chromatography of membrane glycoproteins from chick brain on tenascin-Sepharose, we isolated a major cell surface ligand of 135 kD which we identified as contactin/F11 by NH2-terminal sequencing. The binding specificity between contactin/F11 and tenascin was demonstrated in solid-phase assays. Binding of immunopurified 125I-labeled contactin/F11 to immobilized tenascin is completely inhibited by the addition of soluble tenascin or contactin/F11, but not by fibronectin. When the fractionated isoforms of tenascin were used as substrates, contactin/F11 bound preferentially to the 190-kD isoform. This isoform differs in having no alternatively spliced fibronectin type III domains. Our results imply that the introduction of these additional domains in some way disrupts the contactin/F11 binding site on tenascin. To localize the binding site on contactin/F11, proteolytic fragments were generated and characterized by NH2-terminal sequencing. The smallest contactin/F11 fragment which binds tenascin is 45 kD and also begins with the contactin/F11 NH2-terminal sequence. This implies that contactin/F11 binds to tenascin through a site within the first three Ig-domains.

Amino Acid Sequence↗