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A Carruthers

Publications and source records attributed to A Carruthers.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1998

Hair tie-over dressing. A simple dressing for hair-bearing scalp wounds.

OBJECTIVE: To describe a temporary dressing for Mohs micrographic surgery wounds of the hair-bearing scalp. METHOD: The technique of using hair at the wound edges to hold down the dressing is described. RESULTS: This is an effective, simple, comfortable, and inexpensive scalp dressing, which our patients have found to be very acceptable. CONCLUSION: We consider that the hair tie-over dressing is an ideal temporary dressing for Mohs micrographic surgery wounds of the hair-bearing scalp.

Bandages↗
PubMed1997

Treatment of facial furrows and rhytides.

Many substances have historically been used to address facial soft tissue defects. Currently in the United States autologous fat and injectable bovine collagen are the most commonly utilized injectable fillers. Additionally, the judicious application of BOTOX in the upper face as well as neck has all but revolutionized the use of filling agents in these locales. While other agents are briefly mentioned, this is an in-depth review of the characteristics and application of autologous fat, bovine collagen.

Adult↗
PubMed1997

Botox concerns.

Explore the source record for details and available documents.

Botulinum Toxins, Type A↗
PubMed1997

General practitioner participation in 'Morning Report' at a major teaching hospital.

General practitioners attending 'Morning Report' have provided information on the general practice management of a wide range of conditions and have promoted the benefits of improved communication between general practitioners and hospital doctors. By collecting data on a range of problems at the community hospital interface, they are in a position to identify and act upon issues with important implications for health care. This activity is recommended to all general practitioners working in association with a major hospital.

Humans↗
PubMed1996

Regulation of GLUT1-mediated sugar transport by an antiport/uniport switch mechanism.

Avian erythrocyte sugar transport is stimulated during anoxia and during exposure to inhibitors of oxidative phosphorylation. This stimulation results from catalytic desuppression of the cell surface glucose transporter GLUT1 [Diamond, D., & Carruthers, A. (1993) J. Biol. Chem. 268, 6437-6444]. The present study was undertaken to investigate the mechanisms of GLUT1 suppression/desuppression. Sugar uniport (sugar uptake or exit in the absence of sugar at the opposite side of the membrane) is absent in normoxic avian erythrocytes, but sugar antiport (sugar uptake coupled to sugar exit) is present. Exposure to cyanide and/or to FCCP (mitochondrial inhibitors) stimulates erythrocyte sugar uniport but not sugar antiport. K(m)(app) for 3-O-methylglucose uniport and antiport are unaffected by metabolic poisoning. Ki(app) for inhibitions of 3-O-methylglucose uniport by cytochalasin B and forskolin (sugar export site ligands) are unaffected by progressive stimulation of sugar uniport. Cyanide and FCCP stimulation of 3-O-methylglucose uniport are associated with increased AMP-activated protein kinase activity. Purified human GLUT1 is not phosphorylated by exposure to cytosol extracted from poisoned avian erythrocytes. FCCP does not stimulate GLUT1-mediated 3-O-methylglucose uptake in K562 cells but does increase K562 AMP-activated protein kinase activity. FCCP stimulation of 3-O-methylglucose uniport in resealed erythrocyte ghosts requires cytosolic ATP and/or glutathione. The nonmetabolizable ATP analog AMP-PNP cannot be substituted for ATP in this action. These results are contrasted with allosteric regulation of human erythrocyte sugar transport and suggest that avian erythrocyte sugar transport suppression results from inhibition of carrier uniport function. Uniport suppression is not mediated by interaction with cytosolic molecular species that bind to the sugar export site. The antiport to uniport switch mechanism requires ATP hydrolysis, is associated with elevated AMP-activated kinase function, and, if triggered by this kinase, is mediated by factors absent in K562 cells and downstream from the kinase.

3-O-Methylglucose↗
PubMed1996

Human erythrocyte sugar transport is incompatible with available carrier models.

GLUT1-mediated, passive D-glucose transport in human erythrocytes is asymmetric, Vmax and K(m)(app) for D-glucose uptake at 4 degrees C are 10-fold lower than Vmax and K(m)(app) for D-glucose export. Transport asymmetry is not observed for GLUT1-mediated 3-O-methylglucose transport in rat, rabbit, and avian erythrocytes and rat adipocytes where Vmax for sugar uptake and exit are identical. This suggests that transport asymmetry is either an intrinsic catalytic property of human GLUT1 or that factors present in human erythrocytes affect GLUT1-mediated sugar transport. In the present study we assess human erythrocyte sugar transport asymmetry by direct measurement of sugar transport rates and by analysis of the effects of intra- and extracellular sugars on cytochalasin B binding to the sugar export site. We also perform internal consistency tests to determine whether the measured, steady-state 3-O-methylglucose transport properties of human erythrocytes agree with those expected of two hypothetical models for protein-mediated sugar transport. The simple-carrier hypothesis describes a transporter that alternately exposes sugar import and sugar export pathways. The fixed-site carrier hypothesis describes a sugar transporter that simultaneously exposes sugar import and sugar export pathways. Steady-state 3-O-methylglucose transport in human erythrocytes at 4 degrees C is asymmetric. Vmax and K(m)(app) for sugar uptake are 10-fold lower than Vmax and K(m)(app) for sugar export. Phloretin-inhibitable cytochalasin B binding to intact red cells is unaffected by extracellular D-glucose but is competitively inhibited by intracellular D-glucose. This inhibition is reduced by 13% +/- 4% when saturating extracellular D-glucose levels are also present. Assuming transport is mediated by a simple-carrier and that cytochalasin B and intracellular D-glucose binding sites are mutually exclusive, the cytochalasin B binding data are explained only if transport is almost symmetric (Vmax exit = 1.4 Vmax entry). The cytochalasin B binding data are consistent with both symmetric and asymmetric fixed-site carriers. Analysis of 3-O-methylglucose, 2-deoxy-D-glucose, and D-glucose uptake in the presence of intracellular 3-O-methylglucose, demonstrates significant divergence in experimental and theoretical transport behaviors. We conclude either that human erythrocyte sugar transport is mediated by a carrier mechanism that is fundamentally different from those considered previously or that human erythrocyte-specific factors prevent accurate determination of GLUT1-mediated sugar translocation across the cell membrane. We suggest that GLUT1-mediated sugar transport in all cells is an intrinsically symmetric process but that intracellular sugar complexation in human red cells prevents accurate determination of transport rates.

3-O-Methylglucose↗
PubMed1996

Botulinum A exotoxin use in clinical dermatology.

Botulinum toxin (BT) prevents the release of acetylcholine at the neuromuscular junction and produces reversible paralysis of striated muscle. This effect was initially used for ophthalmologic indications, particularly strabismus. The idea of using the toxin for purely cosmetic purposes arose from the observation that therapy for facial dystonias markedly decreased lines and wrinkles in the treated areas. The ease of application, high safety profile, and impressive results from the cosmetic use of BT have led to its rapid acceptance by many clinicians. As use of BT increases and its indications expand, an understanding of this therapeutic modality is timely. This article discusses the pharmacologic aspects of BT as well as the methods for administration as they relate to its cosmetic use.

Botulinum Toxins↗