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A Carruthers

Publications and source records attributed to A Carruthers.

At least 19 recordsLinked to original sources
PubMed2000

ATP-dependent substrate occlusion by the human erythrocyte sugar transporter.

Human erythrocyte sugar transport presents a functional complexity that is not explained by existing models for carrier-mediated transport. It has been suggested that net sugar uptake is the sum of three serial processes: sugar translocation, sugar interaction with an intracellular binding complex, and the release from this complex into bulk cytosol. The present study was carried out to identify the erythrocyte sugar binding complex, to determine whether sugar binding occurs inside or outside the cell, and to determine whether this binding complex is affected by cytosolic ATP or transporter quaternary structure. Sugar binding assays using cells and membrane protein fractions indicate that sugar binding to erythrocytes is quantitatively accounted for by sugar binding to the hexose transport protein, GluT1. Kinetic analysis of net sugar fluxes indicates that GluT1 sugar binding sites are cytoplasmic. Intracellular ATP increases GluT1 sugar binding capacity from 1 to 2 mol of 3-O-methylglucose/mol GluT1 and inhibits the release of bound sugar into cytosol. Reductant-mediated, tetrameric GluT1 dissociation into dimeric GluT1 is associated with the loss of ATP and 3-O-methylglucose binding. We propose that sugar uptake involves GluT1-mediated, extracellular sugar translocation into an ATP-dependent cage formed by GluT1 cytoplasmic domains. Caged or occluded sugar has three possible fates: (1) transport out of the cell (substrate cycling); (2) interaction with sugar binding sites within the cage, or (3) release into bulk cytosol. We show how this hypothesis can account for the complexity of erythrocyte sugar transport and its regulation by cytoplasmic ATP.

3-O-Methylglucose↗
PubMed2000

Unplanned incomplete Mohs micrographic surgery.

BACKGROUND: Incomplete Mohs micrographic surgery (MMS) is the cessation of MMS while the tumor margins are known to be still positive. OBJECTIVE: Our purpose was to examine the factors behind unplanned incomplete MMS and to identify means of avoiding and managing this situation when it arises. METHODS: We performed a retrospective case review examining clinical presentations, histologic features, and management of incomplete MMS. RESULTS: Fifteen of 10,346 procedures (0.15%) were identified as incomplete MMS. Complete records were available in 14 cases. The age range was 30 to 90 years; the study comprised 10 men and 4 women. The tumors included 9 basal cell and 4 squamous cell carcinomas and 1 dermatofibrosarcoma protuberans. The sites involved were nose, medial canthus, ear, scalp, and lower eyelid. Twelve cases dealt with unresectable disease, whereas two patients were unable to tolerate further surgery. Of the unresectable cases, MMS was terminated because of ongoing multifocal positive skin margins, bony invasion, or extension of tumor to other locations. Surgical defects were repaired, whereas residual disease was managed with a variety of methods. CONCLUSION: Incomplete MMS is a rare problem of either unresectable disease or inability of the patient to tolerate the procedure. Preoperative planning may help to identify both subgroups of patients. A multispecialty approach to managing these cases is often necessary.

Adult↗
PubMed1999

The human erythrocyte sugar transporter presents two sugar import sites.

The human erythrocyte sugar transporter presents sugar import (e2) and sugar export (e1) sites simultaneously. This study asks whether the sugar transporter exposes only one or multiple import sites. We approached this question by analysis of cytochalasin B binding to the human erythrocyte sugar export site in the presence of sugars that bind to the sugar import site. Extracellular maltose does not enter human erythrocytes. High concentrations of maltose (1-100 mM) inhibit cytochalasin B binding to human red cells. Low concentrations (25-500 microM) increase the level of erythrocyte cytochalasin B binding. Maltose modulation of cytochalasin B binding is mediated by altered affinity of sugar export sites for cytochalasin B. Similar results are obtained with other cell-impermeant inhibitors of sugar uptake. Extracellular D-glucose (a transported sugar) stimulates cytochalasin B binding at low D-glucose concentrations (10-250 microM), but this effect is lost at higher concentrations. Intracellular D-glucose inhibits cytochalasin B binding. Low concentrations of extracellular maltose and other nontransported inhibitors stimulate 3-O-methylglucose uptake in erythrocytes. Higher sugar concentrations (1-100 mM) inhibit transport. These data support the hypothesis that the erythrocyte sugar transporter presents two sugar import sites and at least one sugar export site. This conclusion is consistent with the proposed oligomeric structure of the sugar transporter, a complex of four GluT1 proteins in which each subunit presents a translocation pathway.

3-O-Methylglucose↗
PubMed1999

Stop-flow analysis of cooperative interactions between GLUT1 sugar import and export sites.

The human erythrocyte sugar transporter is thought to function either as a simple carrier (sugar import and sugar export sites are presented sequentially) or as a fixed-site carrier (sugar import and sugar export sites are presented simultaneously). The present study examines each hypothesis by analysis of the rapid kinetics of reversible cytochalasin B binding to the sugar export site in the presence and absence of sugars that bind to the sugar import site. Cytochalasin B binding to the purified, human erythrocyte glucose transport protein (GLUT1) induces quenching of GLUT1 intrinsic tryptophan fluorescence. The time-course of GLUT1 fluorescence quenching reflects a second-order process characterized by simple exponential kinetics. The pseudo-first-order rate constant describing fluorescence decay (kobs) increases linearly with [cytochalasin B] while the extent of fluorescence quenching increases in a saturable manner with [cytochalasin B]. Rate constants for cytochalasin B binding to GLUT1 (k1) and dissociation from the GLUT1.cytochalasin B complex (k-1) are obtained from the relationship: kobs = k-1 + k1[cytochalasin B]. Low concentrations of maltose, D-glucose, 3-O-methylglucose, and other GLUT1 import-site reactive sugars increase k-1(app) and reduce k1(app) for cytochalasin B interaction with GLUT1. Higher sugar concentrations decrease k1(app) further. The simple carrier mechanism predicts that k1(app) alone is modulated by import- and export-site reactive sugars and is thus incompatible with these findings. These results are consistent with a fixed-site carrier mechanism in which GLUT1 simultaneously presents cooperative sugar import and export sites.

3-O-Methylglucose↗
PubMed1999

Randomized controlled trial of a computer strategy to increase general practitioner preventive care.

BACKGROUND: Previous interventions targeting primary care practitioners with the aim of increasing preventive care delivery have demonstrated limited effectiveness. The primary aim of this study was to assess the effectiveness of a computerized continuing medical education program to increase rates of three screening behaviors (cholesterol, blood pressure, and cervical screening) and to identify three risk behaviors (smoking, alcohol consumption, benzodiazepine use) in general practice. METHODS: Nineteen general practitioners were randomly allocated to intervention or control conditions. Those given the intervention received a computerized feedback system. The intervention was delivered using a touch-screen computer located in the surgery waiting area. The preventive behaviors of interest were patient smoking, alcohol use, benzodiazepine use, and blood pressure, cholesterol and cervical screening using the Papanicolou test. Differences in performance by group in each of the outcomes was measured at baseline and 3-month follow-up. Logistic regression analyses with generalized estimating equations were conducted as the main analyses. RESULT: At 3-month follow-up, statistically significant differences were evident in the following outcome measures: accurate classification of benzodiazepine users (z = 2.8540, P < 0.05); accurate classification of non-benzodiazepine users (z = 2.7339, P < 0.05); accurate classification of hazardous or harmful alcohol drinkers (z = 2.3079, P < 0.02); blood pressure screening (z = 3.4136, P < 0.001); and cholesterol screening (z = 6.6313, P < 0.001). CONCLUSION: A computerized system of performance-specific feedback was effective at increasing some preventive care services in general practice.

Adult↗
PubMed1999

Raising eyebrows with botulinum toxin.

BACKGROUND: Brow elevation rejuvenates the facial appearance. OBJECTIVE: To determine if a significant degree of brow elevation could be achieved through selective botulinum toxin treatment of brow depressors. METHODS: Seven women aged 31-42 (mean 37) years old were treated. The distance from lowest eyebrow cilium of the eyebrow to the midpupillary point was measured before and 1 month posttreatment. Botulinum toxin was injected into the glabellar area (7-10U) and the supralateral eyebrow (0-2.5U each side), to a total dose of 10-14 U. RESULTS: Five individuals (71%) showed brow elevation of 1-3 mm with a mean elevation of 1 mm. Two individuals showed no change. Concurrent weakening of the frown response was noted in all patients. CONCLUSION: Botulinum toxin treatment of brow depressors produces a small degree of brow elevation in the majority of patients.

Adult↗
PubMed1999

Electrosurgical skin resurfacing: a new bipolar instrument.

BACKGROUND: Numerous modalities may be used for skin resurfacing, including chemical peels, dermabrasion, and lasers. Each of these methods is associated with significant disadvantages. OBJECTIVE: The purpose of these initial studies was to determine the efficacy and safety of a new electrosurgical resurfacing system. Depth of cutaneous injury was also evaluated. METHODS: Postoperative scar resurfacing was performed on six patients in the initial feasibility study. Patients were evaluated with questionnaires, physician observations, and photographs. The histologic investigation evaluated depth of injury after resurfacing at various power settings and number of passes. RESULTS: Appearance of postoperative scars in all 6 patients was improved by electrosurgical resurfacing. The overall injury, residual thermal damage plus ablation, for all power levels and passes was 114.1 micrometer (mean) with a standard deviation of 60.7 micrometer. CONCLUSION: Electrosurgical resurfacing may become an effective and safe alternative to current resurfacing modalities.

Adult↗
PubMed1999

Malar fat pad elevation: An aid to closure.

BACKGROUND: In closure of defects inferior to the eye, it is important to avoid inducing lower lid ectropion. OBJECTIVE: To describe a new technique for closure of defects inferior and lateral to the eye. METHODS: A case of malar fat pad elevation to close a post-Mohs surgical defect is described and the procedure is detailed. RESULTS: This technique enabled good wound closure with minimal tension and avoided the complication of ectropion. A transient asymmetry was manifest postoperatively. CONCLUSION: Malar fat pad elevation is an effective and elegant means of closing defects inferior and lateral to the eye. This technique minimizes extensive tissue undermining and movement with its consequences of postoperative tissue swelling, bruising, and hematoma formation. The side effect of ectropion is prevented.

Adipose Tissue↗
PubMed1999

Update on Botulinum Toxin.

Botulinum toxin type-A (BTX-A) is a neurotoxin which blocks presynaptic release of acetylcholine. It interferes with neuromuscular transmission, temporarily paralyzing the affected muscle. Of special interest for dermatologists is the unlabelled cosmetic applications, for conditions such as wrinkles and hyperhidrosis. Labelled indications in Europe are for cervical dystonia and cerebral palsy. In the US, it is approved for treatment of strabismus, blepharospasm and hemifacial spasm in adults. After repeated use of high doses, antibodies can develop in some individuals, making further treatment ineffective indefinitely. Even when used in high does for neurological conditions, the development of antibodies occurs in < 5&percnt of patients. In 1997, the US FDA approved a new bulk toxin source for use in the manufacture of BTX-A. It has a higher specific potency than original BTX-A formulations, reducing the amount of utilized neurotoxin protein, and thereby reducing antibody production. Another form of this neurotoxin (type B) also appears to be effective in patients who have developed antibodies to BTX-A. It is awaiting US FDA approval for treatment of cervical dystonia.

Journal Article↗
PubMed1998

Structural and physiologic determinants of human erythrocyte sugar transport regulation by adenosine triphosphate.

Human erythrocyte sugar transport is mediated by the integral membrane protein GLUT1 and is regulated by cytosolic ATP [Carruthers, A., and Helgerson, A. L. (1989) Biochemistry 28, 8337-8346]. This study asks the following questions. (1) Where is the GLUT1 ATP binding site? (2) Is ATP-GLUT1 interaction sufficient for sugar transport regulation? (3) Is ATP modulation of transport subject to metabolic control? GLUT1 residues 301-364 were identified as one element of the GLUT1 ATP binding domain by peptide mapping and N-terminal sequence analysis of proteolytic fragments of azidoATP-photolabeled GLUT1. Nucleotide binding and sugar transport experiments undertaken with dimeric and tetrameric forms of GLUT1 indicate that only tetrameric GLUT1 binds and is subject to modulation by ATP. Reconstitution experiments indicate that nucleotide and tetrameric GLUT1 are sufficient for ATP modulation of sugar transport. Feedback control of GLUT1 regulation by ATP was investigated by measuring sugar uptake into erythrocyte ghosts containing or lacking ATP and glycolytic intermediates. Only AMP and ADP modulate ATP regulation of transport. Reduced cytosolic pH inhibits ATP modulation of GLUT1-mediated 3OMG uptake and increases Kd(app) for ATP interaction with GLUT1. We conclude that tetrameric but not dimeric GLUT1 is subject to direct regulation by cytosolic ATP and that this regulation is antagonized by intracellular AMP and acidification.

Adenosine Triphosphate↗
PubMed1998

Clinical indications and injection technique for the cosmetic use of botulinum A exotoxin.

BACKGROUND: Some wrinkles and unsightly facial expressions are due to overactivity of the underlying facial musculature. Botulinum A exotoxin reversably paralyses selected muscles. Botulinum toxin has been used to correct facial cosmetic concerns. OBJECTIVES: This paper describes the authors' experience with the cosmetic use of botulinum toxin. The areas that can be treated, the appropriate technique for each area and special considerations such as dose, dilution, and relevant anatomy are discussed. RESULTS: Our results have been published previously and are referenced in this paper. CONCLUSIONS: Botulinum toxin is safe and effective in the management of some facial lines and wrinkles. Its use is associated with a high degree of patient and physician satisfaction.

Botulinum Toxins, Type A↗
PubMed1998

The adjunctive usage of botulinum toxin.

BACKGROUND: Botulinum toxin is a safe, helpful adjunct to many other treatments for facial rejuvenation. Used together, the final result is more polished and refined. In addition, botulinum toxin can be used to maintain the surgical laser results by preventing dynamic facial muscular action re-establishing expressive wrinkles and folds. OBJECTIVES: We describe the facial areas best treated with botulinum toxin and our adjunctive techniques so that the cosmetic physician can easily incorporate these into their practice. RESULTS: The aesthetic results are improved with the combination of botulinum toxin and the surgical or laser procedure over either modality alone. CONCLUSIONS: We believe that there are many new treatment options for combined therapy with botulinum toxin, laser resurfacing, and surgical procedure in periocular and facial rejuvenation that the aesthetic physician can easily incorporate into their practice.

Blepharoplasty↗
PubMed1998

Membrane-bound glyceraldehyde-3-phosphate dehydrogenase and multiphasic erythrocyte sugar transport.

Net sugar import by human erythrocytes consists of ATP-modulated rapid and slow phases while sugar export consists of a single slow phase. We have proposed that this behaviour results from obligate substrate tunnelling from transporter to bulk cytosol through a complex containing high-affinity, low-capacity sugar binding sites (Cloherty, Sultzman, Zottola & Carruthers, 1995). Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) is known to compartmentalize ATP delivery to erythrocyte membrane ATPases and interact directly with the erythrocyte glucose transporter in vitro. The present study examines the possibility that GAPDH is an obligate component of the hypothesized sugar-binding complex. GAPDH remains associated with the erythrocyte membrane following cell lysis and remains associated with the cytoskeleton under conditions where more than 99% of the membrane glucose transport protein (GLUT1) is released by detergent (Triton X-100). GAPDH is released from erythrocyte membranes upon exposure to Mg.ATP or to NADH. ATP displacement of membrane-bound GAPDH is half-maximal at 200 microM ATP and appears to involve ATP interaction with multiple, co-operative sites. GAPDH interaction with purified tetrameric GLUT1 is saturable, co-operative and also inhibited by ATP. ATP inhibition of GAPDH binding to purified tetrameric GLUT1 is less effective than ATP inhibition of GAPDH binding to intact erythrocyte membranes. Removal of cellular GAPDH by exposing erythrocyte membranes to NADH prior to membrane resealing neither affects ATP modulation of sugar transport nor reduces biphasic net sugar uptake to a single phase. We conclude that ATP-sensitive GAPDH interaction with the cytoplasmic surface of erythrocyte membranes and GLUT1 is responsible neither for ATP modulation of sugar transport nor for multiphasic net sugar import by human red cells.

3-O-Methylglucose↗
PubMed1998

Basal cell carcinoma of the periocular region.

BACKGROUND: Basal cell carcinomas of the periocular area present a particular challenge because of the likelihood of damage to vital structures. OBJECTIVE: More than 10-years experience of treating basal cell carcinomas by Mohs micrographic surgery was reviewed. METHODS: Chart analysis of 233 periocular basal cell carcinomas was performed. All patients were contacted either in clinical follow-up or by telephone review. RESULTS: Two hundred and thirty-three periocular basal cell carcinomas were analyzed out of a total of 3, 192 basal cell carcinomas treated during this period (7.3%). Patients ranged in age from 17 to 102 years with a mean age of 58.8 years and a median of 59.0 years. Of the patients, 54.5% were female. Mohs micrographic surgery was the prime therapy in 177 patients (75. 9%). Of the lesions, 48.5% occurred in the medial canthal area, 35. 2% on the lower eyelid, 10.7% on the upper eyelid, and 5.6% on the lateral canthus. There was no significant difference between the left/right distribution in males and females. The average follow-up time was 34 months (standard deviation 26.38 months). A cumulative rate of no recurrence tabulated by modified life table analysis was 0.9864. CONCLUSION: This study further documents the problems associated with basal cell carcinoma of the periocular area as well as the value of Mohs micrographic surgery as treatment.

Adolescent↗