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Biomedical subjects

J C Jones

Publications and source records attributed to J C Jones.

At least 55 records · Page 3Linked to original sources

Vagus nerve stimulation therapy for partial-onset seizures: a randomized active-control trial.

OBJECTIVE: The purpose of this multicenter, add-on, double-blind, randomized, active-control study was to compare the efficacy and safety of presumably therapeutic (high) vagus nerve stimulation with less (low) stimulation. BACKGROUND: Chronic intermittent left vagus nerve stimulation has been shown in animal models and in preliminary clinical trials to suppress the occurrence of seizures. METHODS: Patients had at least six partial-onset seizures over 30 days involving complex partial or secondarily generalized seizures. Concurrent antiepileptic drugs were unaltered. After a 3-month baseline, patients were surgically implanted with stimulating leads coiled around the left vagus nerve and connected to an infraclavicular subcutaneous programmable pacemaker-like generator. After randomization, device initiation, and a 2-week ramp-up period, patients were assessed for seizure counts and safety over 3 months. The primary efficacy variable was the percentage change in total seizure frequency compared with baseline. RESULTS: Patients receiving high stimulation (94 patients, ages 13 to 54 years) had an average 28% reduction in total seizure frequency compared with a 15% reduction in the low stimulation group (102 patients, ages 15 to 60 year; p = 0.04). The high-stimulation group also had greater improvements on global evaluation scores, as rated by a blinded interviewer and the patient. High stimulation was associated with more voice alteration and dyspnea. No changes in physiologic indicators of gastric, cardiac, or pulmonary functions occurred. CONCLUSIONS: Vagus nerve stimulation is an effective and safe adjunctive treatment for patients with refractory partial-onset seizures. It represents the advent of a new, nonpharmacologic treatment for epilepsy.

Adolescent↗

A microbiological investigation following the disinfection of alginate and addition cured silicone rubber impression materials.

The antimicrobial efficacy of four commercially available disinfectants (Haz-tabs, chlorhexidine, Virkon and C&J Algisept Spray) was investigated. It was shown that all were effective in decontaminating the impressions whilst those placed only in sterile water, used as a control, showed variable levels of bacterial growth. Moreover, alginate appeared to carry significantly higher numbers of bacteria than addition cured silicone rubber.

Adult↗

The effect of disinfecting alginate and addition cured silicone rubber impression materials on the physical properties of impressions and resultant casts.

Four commercially available disinfectants were tested and the dimensional stability and detail reproduction of impressions and their resultant casts were measured according to ANSI/ISO specifications. Results showed that alginate impressions immersed in chlorhexidine exhibited considerable dimensional change if not poured immediately. Moreover, alginate impressions soaked in a paraldehyde agent (Virkon) for more than 2 minutes produced casts of inferior surface quality whilst those sprayed and left in contact with phenol derivatives (C&J Spray) for 30 minutes resulted in casts which demonstrated statistically and clinically significant dimensional changes. Addition cured silicone impressions exhibited minimal dimensional change regardless of the disinfection regime employed and the resultant casts were accurate with acceptable surface quality.

Alginates↗

Laminin-5 and modulation of keratin cytoskeleton arrangement in FG pancreatic carcinoma cells: involvement of IFAP300 and evidence that laminin-5/cell interactions correlate with a dephosphorylation of alpha 6A integrin.

Under normal culture conditions, epithelial cells of the FG line, derived from a pancreatic tumor, characteristically grow in mounds and fail to flatten efficiently onto their substrate. In such cells, keratin intermediate filaments (IFs) are concentrated in the perinuclear region. Furthermore, the IF associated protein, IFAP300, primarily localizes along these keratin bundles. Additionally, alpha 6 beta 4 integrin heterodimers localize in streaks or spots towards the edges of cells while alpha 3 beta 1 integrin is predominantly at cell-cell surfaces. Neither show any obvious interaction with IF. Remarkably, upon plating FG cells into medium containing soluble rat laminin-5, FG cells rapidly adhere and spread onto their substrate. Moreover, FG cells "capture" rat laminin-5 and place it basally in circles or arcs at areas of cell-substrate interaction. Double label immunofluorescence microscopy reveals colocalization of IFAP300 as well as alpha 6 beta 4 and alpha 3 beta 1 integrin with the polarized laminin-5. Concomitantly, alpha 6 integrin undergoes dephosphorylation on serine residue 1041. Laminin-5-induced rapid adhesion can be blocked by antibodies against the alpha 3 integrin subunit. In contrast, while alpha 6 integrin antibodies do not block laminin-5-induced rapid adhesion, they prevent FG cells from assuming an epithelial-like morphology. Keratin IF bundles associate with IFAP300-alpha 6 beta 4/alpha 3 beta 1 integrin complexes along the cell-substratum-attached surface of FG cells coincubated in laminin-5-containing medium. Coprecipitation results suggest that in these complexes, IFAP300 may associate with the alpha 6 beta 4 integrin heterodimer. Based on our results and published evidence that IFAP300 binds keratin in vitro [Skalli et al., 1994; J. Cell Biol. 125:159-170], we propose that laminin-5/FG cell interaction results in a novel integrin dephosphorylation event, which subsequently induces IFAP300 association with alpha 6 beta 4 integrin. IFAP300 then mediates the interaction of IFs with the cell surface via the alpha 6 beta 4 integrin heterodimer.

Amino Acid Sequence↗

When do sphenoidal electrodes yield additional data to that obtained with antero-temporal electrodes?

The advantage of using sphenoidal (SE) over antero-temporal electrodes (ATE) remains controversial among epileptologists. Yet, in a recently published study of 17 patients with seizures of antero-temporal origin (Kanner et al., 1995), we demonstrated that SE placed under fluoroscopic guidance (FPSE), in order to insure that their recording tips are positioned immediately below the foramen ovale (FO), yielded a significant advantage over SE placed with the standard blind method of insertion (BPSE), in both interictal and ictal recordings. This study was done to test the following hypothesis: FPSE advantage over BPSE and ATE resides in the recording of epileptiform activity with a restricted electric field. We compared spike voltages at FPSE, BPSE and ATE in sets of 5 randomly selected spikes per interictal focus, recorded in the course of separate monitoring studies with BPSE and FPSE. We represented the voltage differences as ratios, VATE/FPSE and VATE/BPSE and calculated a mean ratio for each spike set. The spikes' voltage was almost identical at BPSE and at ATE (mean VATE/BPSE = 0.94), while it was significantly higher at FPSE than at ATE (mean VATE/FPSE = 0.66; P < 0.001, t test). A significantly narrower electric field contour was found among interictal foci in which FPSE yielded additional data during interictal (P < 0.001) and ictal (P = 0.016) recordings. Conversely, VATE/FPSE did not differ from VATE/BPSE among interictal foci where FPSE failed to yield any advantage over BPSE in either interictal (P = 0.240), or ictal (P = 0.311) recordings. These findings prove that SE yield additional localizing data when recording epileptiform activity with a restricted field, provided that its recording tip is positioned below the FO. When distant from FO, SE can be expected to yield comparable data to that obtained with ATE.

Action Potentials↗

Coating of titanium alloy with soluble laminin-5 promotes cell attachment and hemidesmosome assembly in gingival epithelial cells: potential application to dental implants.

The formation of a biological seal around the transmucosal portion of dental implants may be crucial for the long-term success of these therapies. Data to date suggest that the gingival epithelium attaches to dental implants through the formation of hemidesmosomes. Biochemical and genetic data indicate that the laminin isoform, laminin-5, a component of basement membranes, plays a crucial role in the assembly and maintenance of hemidesmosomes. We report the use of soluble laminin-5 as a biological coating of titanium-alloy to promote cell attachment of the gingival epithelial cell line, IHGK. Monoclonal antibodies reactive with laminin-5 depleted the coating solution of all cell attachment activity and blocked cell attachment to laminin-5-coated disks. Immunodepletion with antibodies to fibronectin had no effect. Finally, we demonstrate that IHGK cells assembled hemidesmosomes within 24 h of attachment to laminin-5-coated titanium alloy but not to the titanium alloy alone. These results suggest that soluble laminin-5 may have clinical applications as a dental implant coating to promote the formation of a biological seal.

Alloys↗

The role of laminin-5 and its receptors in mammary epithelial cell branching morphogenesis.

In vivo, normal mammary epithelial cells utilize hemidesmosome attachment devices to adhere to stroma. However, analyses of a potential role for hemidesmosomes and their components in mammary epithelial tissue morphogenesis have never been attempted. MCF-10A cells are a spontaneously immortalized line derived from mammary epithelium and possess a number of characteristics of normal mammary epithelial cells including expression of hemidesmosomal associated proteins such as the two bullous pemphigoid antigens, alpha 6 beta 4 integrin and its ligand laminin-5. More importantly, MCF-10A cells readily assemble mature hemidesmosomes when plated onto uncoated substrates. When maintained on matrigel, like their normal breast epithelial cell counterparts, MCF-10A cells undergo a branching morphogenesis and assemble hemidesmosomes at sites of cell-matrigel interaction. Function blocking antibodies specific for human laminin-5 and the alpha subunits of its two known receptors (alpha 3 beta 1 and alpha 6 beta 4 integrin) not only inhibit hemidesmosome assembly by MCF-10A cells but also impede branching morphogenesis induced by matrigel. Our results imply that the hemidesmosome, in particular those subunits comprising its laminin-5/integrin 'backbone', play an important role in morphogenetic events. We discuss these results in light of recent evidence that hemidesmosomes are sites involved in signal transduction.

Antibodies↗

Use of psychotropic medication in Oklahoma: a statewide survey.

Analysis of statewide survey data revealed that 22.5% of individuals with mental retardation who were served by the Oklahoma mental retardation system were receiving antipsychotic medication. Anxiolytic medications were prescribed for 9.3%, and antidepressants were prescribed for 5.9%. Higher levels of medication use were found in institutional settings and Intermediate Care Facility settings.

Adolescent↗

Morphogenetic effects of soluble laminin-5 on cultured epithelial cells and tissue explants.

The rat cell line 804G assembles an extracellular matrix which induces not only the rapid adhesion and spreading of epithelial cells but also the assembly of a cell-matrix attachment device called the hemidesmosome. The major component of this matrix is laminin-5. We have purified rat laminin-5 from medium conditioned by 804G cells. Epithelial cells which are co-incubated with medium supplemented with soluble laminin-5 adhere and spread rapidly. Furthermore, human carcinoma cells undergo a dramatic morphologic change in the presence of laminin-5 and form orderly arrays resembling epithelial sheets. Soluble rat laminin-5 is selectively incorporated into an insoluble matrix of epithelial cells in vitro, since rat-specific laminin-5 antibodies stain cell-substrate contacts. Addition of medium containing soluble laminin-5 to explanted, human corneal rims induces assembly of hemidesmosomes, important cell-matrix attachment devices. Furthermore, rat-specific laminin-5 antibodies stain areas of contact between corneal epithelium and basement membrane, indicating that rat laminin-5 from the medium is incorporated into basement membrane. We discuss the use of laminin-5 as a medium supplement for the culture of both epithelial cells and epithelial tissue explants.

Animals↗

Effect of a high-protein meal on gabapentin pharmacokinetics.

The anticonvulsant gabapentin is transported across biological membranes via the L-amino acid transport system (System-L). Absorption of gabapentin is saturable, and in-vitro data have previously demonstrated that both L-leucine and L-phenylalanine may compete with the intestinal transport of gabapentin. The purpose of this study therefore was to determine whether a high-protein meal would interfere with gabapentin absorption. Ten healthy volunteers received in a randomized, cross-over design, a single 600-mg dose of gabapentin in the fasting state and after a high-protein meal consisting of 80 gm total protein (4.1 g phenylalanine, 8.2 g leucine and 4.2 g isoleucine), 52 g carbohydrate, and 9 g fat. Plasma gabapentin concentrations were measured by HPLC at baseline, 0.25, 0.5, 0.75, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 6, 8, 12, 24, 30 h. Calculated pharmacokinetic parameters included Cmax' Tmax' AUC and T1/2. In addition, a pharmacodynamic assessment (using visual analog scales) of gabapentin-related adverse effects was performed at 2 h post drug ingestion and was compared between study phases. Statistical analysis included Student's t-test for paired data, with significance assigned at P < 0.05. Cmax was significantly increased by 36% (3.87 +/- 1.15 vs 5.28 +/- .97 micrograms/ml, P = 0.002), and Tmax tended to be shorter (3.9 +/- 1.8 vs 2.8 +/- .35 h, P = 0.10), after the high-protein meal. Although AUC was increased by 11%, this did not achieve statistical significance. Despite significantly higher plasma concentrations at 2 h, subjects reported significantly fewer adverse effects after the high-protein meal. Potential mechanisms to explain these unexpected findings may be that the large amino acid load delivered with the high-protein meal enhanced gabapentin absorption via trans-stimulation, the process by which acutely increased intestinal luminal amino acid concentrations result in an acute up regulation in System-L activity. Conversely, the decrease in perceived adverse CNS effects of gabapentin following the high-protein meal may reflect CNS competition for System-L transport.

Acetates↗

Desmosomes and hemidesmosomes: structure and function of molecular components.

Desmosomes and hemidesmosomes are the major cell surface attachment sites for intermediate filaments at cell-cell and cell-substrate contacts, respectively. The transmembrane molecules of the desmosome belong to the cadherin family of calcium-dependent adhesion molecules, whereas those in the hemidesmosome include the integrin class of cell matrix receptors. In each junction, the cytoplasmic domains of certain transmembrane junction components contain unusually long carboxy-terminal tails not found in those family members involved in linkage of actin to the cell surface. These domains are thought to be important for the regulation of junction assembly and specific attachment of intermediate filaments via associated adapter proteins. Recent developments have suggested the exciting possibility that these junctions, in addition to playing an important structural function in tissue integrity, are both acceptors and affectors of cell signaling pathways. Many desmosomal and hemidesmosomal constituents are phosphoproteins and in certain cases the function of specific phosphorylation sites in regulating protein-protein interactions is being uncovered. In addition, a more active role in transmitting signals that control morphogenesis during development and possibly even regulate cell growth and differentiation are being defined for cytoplasmic and membrane components of these junctions.

Animals↗

Pityrosporum ovale (Malassezia furfur) as the causative agent of seborrhoeic dermatitis: new treatment options.

Several studies indicate that Pityrosporum ovale plays an important role in seborrhoeic dermatitis. Many of these are treatment studies which describe the effectiveness of antimycotics, paralleled by a reduction in the number of P. ovale colonies and then recolonization, leading to a recurrence of seborrhoeic dermatitis. In this study 20 patients with seborrhoeic dermatitis of the scalp were treated with terbinafine (Lamisil) 1% solution once daily for 4 weeks. Eleven of 18 patients (61%) were cured and they were still free of lesions 2 weeks after stopping treatment. No side-effects related to treatment were seen. There was also a significant reduction in the number of P. ovale colonies. This may explain both the good clinical effect and the observation that all patients who were cleared of P. ovale were still free of lesions 2 weeks after stopping treatment.

Adolescent↗

Botulinum toxin--a possible new treatment for axillary hyperhidrosis.

The inhibitory action of botulinum toxin is not limited to the neuromuscular junction. The toxin also blocks the autonomic cholinergic fibres, including the sympathetic fibres to sweat glands. We have previously demonstrated that the toxin produces localized anhidrosis. To determine the dosage, pattern and duration of the anhidrotic effect of botulinum toxin and to test the efficacy of axillary injections, we further studied seven healthy volunteers. Two individuals had subcutaneous injections of botulinum toxin (20 mouse units, Dysport-Porton Products) in the dorsum of the hand. Five healthy volunteers had 15-50U of botulinum toxin A (Botox) injected in one axilla. A circular area of complete anhidrosis on the dorsum of the hand was evident on day 2 and persisted for 11 months. By day 3, two of the axillae (injected with 50 U each) were totally dry and in one (injected with 30 U) the sweating was substantially reduced. The effect persisted for 6-8 months before wearing off. No effect was appreciated in two axillae (injected with 15 and 20 U). No significant side-effects were encountered. Subcutaneous injections of botulinum toxin causes chemodenervation of the sweat glands. In normal individuals axillary sweating can be abolished by 50 U of botulinum toxin A (Botox). The results offer a possible novel treatment for severe cases of axillary hyperhidrosis.

Adult↗

Laminin-5 and hemidesmosomes: role of the alpha 3 chain subunit in hemidesmosome stability and assembly.

Hemidesmosomes are complex macromolecular structures which integrate elements of the extracellular matrix and the cytoskeleton of epithelial cells. To characterize cell-matrix interactions in the hemidesmosome, we have made use of 804G cells which possess the unusual ability to assemble hemidesmosomes in vitro. During the course of our studies, we have raised a set of monoclonal antibodies against rat laminin-5, the major structural element comprising 804G matrix. One of these, termed CM6, recognizes the 150 kDa alpha chain of rat laminin-5 and binds the globular (G) domain of intact laminin-5 molecules as determined by rotary shadowing. CM6 antibodies perturb formed hemidesmosomes in 804G cells. In particular, within 1 hour of incubation of 804G cells with CM6 antibodies, colocalization of laminin-5 and alpha 6 beta 4 integrin is lost and by 2 hours, staining generated by hemidesmosomal antibodies appears primarily cytoplasmic in the perinuclear zone. Ultrastructurally, CM6 antibodies first appear to induce detachment of hemidesmosomes from the underlying matrix. Next, portions of the basal cell surface invaginate to form vesicles whose cytoplasmic-facing surface is coated with hemidesmosomes still associated with keratin intermediate filaments. Anchoring filaments extend into the inside compartment of the vesicles. We have also studied the impact of CM6 antibodies on a model system in which the matrix of 804G cells induces de novo assembly of hemidesmosomes in human keratinocytes. This process involves the plasma membrane reorganization of the hemidesmosome associated integrin alpha 6 beta 4 as well as a redistribution of other hemidesmosome components such as the 230 kDa bullous pemphigoid antigen. Pretreatment of 804G matrix with CM6 antibodies blocks such plasma membrane reorganization of hemidesmosome components and inhibits hemidesmosome formation. Our studies indicate a crucial role for the G domain of the alpha chain of laminin-5 in both nucleation of hemidesmosome assembly as well as maintenance of hemidesmosome structural integrity.

Amino Acid Sequence↗

Changes in expression of monoclonal antibody epitopes on laminin-5r induced by cell contact.

Laminin-5r is a basement membrane component that promotes rapid adhesion and hemidesmosome formation in epithelial cells. We raised monoclonal antibodies and identified their corresponding epitopes on the constituent chains of laminin-5r by western blotting. Using a combination of immunoprecipitation and ELISA assays, we determined that these epitopes are differentially exposed on two forms of the laminin-5r heterotrimer: soluble (passively adsorbed onto plastic) and cell-associated. Antibody 5C5 epitope is exposed on the cell-associated form, but not the soluble/passively adsorbed form of laminin-5r. Epitopes reactive with antibodies CM6, FM3, and TR1 are also preferentially exposed on cell-associated laminin-5r, such that reactivity of these antibodies with the cell-associated form is fourfold higher than with the soluble/passively adsorbed form in ELISA assays. Incubation of passively adsorbed laminin-5r with the human epithelial cell line SCC12 induced exposure of 5C5 and CM6, FM3, or TR1 epitopes. These data suggest that cells actively modify laminin-5r, perhaps during matrix assembly, and that the 5C5 epitope may serve as a marker for assembled laminin-5r matrix.

Animals↗