Sinan Ali - Academia.edu (original) (raw)
Papers by Sinan Ali
International Conference on Spinal Manipulation, 2002
2 page(s
PROTEOMICS, 2012
Human sex hormone binding globulin (hSHBG) is a serum glycoprotein central to the transport and t... more Human sex hormone binding globulin (hSHBG) is a serum glycoprotein central to the transport and targeted delivery of sex hormones to steroid-sensitive tissues. Several molecular mechanisms of action of hSHBG, including the function of its attached glycans remain unknown. Here, we perform a detailed site-specific characterization of the N- and O-linked glycosylation of serum-derived hSHBG. MS-driven glycoproteomics and glycomics combined with exoglycosidase treatment were used in a bottom-up and top-down manner to determine glycosylation sites, site-specific occupancies and monosaccharide compositions, detailed glycan structures, and the higher level arrangement of glycans on intact hSHBG. It was found that serum-derived hSHBG is N-glycosylated at Asn(351) and Asn(367) with average molar occupancies of 85.1 and 95.3%, respectively. Both sites are occupied by the same six sialylated and partly core fucosylated bi- and triantennary N-Glycoforms with lactosamine-type antennas of the form (±NeuAcα6)Galβ4GlcNAc. N-Glycoforms of Asn(367) were slightly more branched and core fucosylated than Asn(351) N-glycoforms due probably to a more surface-exposed glycosylation site. The N-terminal Thr(7) was fully occupied by the two O-linked glycans NeuAcα3Galβ3(NeuAcα6)GalNAc (where NeuAc is N-acetylneuraminic acid and GalNAc is N-acetylgalactosamine) and NeuAcα3Galβ3GalNAc in a 1:6 molar ratio. Electrophoretic analysis of intact hSHBG revealed size and charge heterogeneity of the isoforms circulating in blood serum. Interestingly, the size and charge heterogeneity were shown to originate predominantly from differential Asn(351) glycan occupancies and N-glycan sialylation that may modulate the hSHBG activity. To date, this work represents the most detailed structural map of the heterogeneous hSHBG glycosylation, which is a prerequisite for investigating the functional aspects of the hSHBG glycans.
Molecular & Cellular Proteomics, 2011
Human corticosteroid-binding globulin (CBG), a heavily glycosylated protein containing six N-link... more Human corticosteroid-binding globulin (CBG), a heavily glycosylated protein containing six N-linked glycosylation sites, transports cortisol and other corticosteroids in blood circulation. Here, we investigate the biological importance of the N-glycans of CBG derived from human serum by performing a structural and functional characterization of CBG N-glycosylation. Liquid chromatography-tandem MS-based glycoproteomics and glycomics combined with exoglycosidase treatment revealed 26 complex type N-glycoforms, all of which were terminated with ␣2,3-linked neuraminic acid (NeuAc) residues. The CBG N-glycans showed predominantly bi-and tri-antennary branching, but higher branching was also observed. N-glycans from all six N-glycosylation sites were identified with high site occupancies (70.5-99.5%) and glycoforms from all sites contained a relatively low degree of core-fucosylation (0-34.9%). CBG showed site-specific glycosylation and the site-to-site differences in core-fucosylation and branching could be in silico correlated with the accessibility to the individual glycosylation sites on the maturely folded protein. Deglycosylated and desialylated CBG analogs were generated to investigate the biological importance of CBG N-glycans. As a functional assay, MCF-7 cells were challenged with native and glycan-modified CBG and the amount of cAMP, which is produced as a quantitative response upon CBG binding to its cell surface receptor, was used to evaluate the CBG:receptor interaction. The removal of both CBG N-glycans and NeuAc residues increased the production of cAMP significantly. This confirms that N-glycans are involved in the CBG:receptor interaction and indicates that the modulation is performed by steric and/or electrostatic means through the terminal NeuAc residues.
Memory (Hove, England), Oct 23, 2015
For eyewitness testimony to be considered reliable, it is important to ensure memory remains accu... more For eyewitness testimony to be considered reliable, it is important to ensure memory remains accurate following the event. As many testimonies involve traumatic, as opposed to neutral, events, it is important to consider the role of distress in susceptibility to false memories. The aim of this study was to investigate whether cortisol response following a stressor would be associated with susceptibility to false memories. Psychological distress responses were also investigated, specifically, dissociation, intrusions, and avoidance. Participants were allocated to one of three conditions: those who viewed a neutral film (N = 35), those who viewed a real trauma film (N = 35), and a trauma "reappraisal" group where participants were told the film was not real (N = 35). All received misinformation about the film in the form of a narrative. Participants provided saliva samples (to assess cortisol) and completed distress and memory questionnaires. Cortisol response was a signific...
2014 IEEE International Conference on Control System, Computing and Engineering (ICCSCE 2014), 2014
The challenge of removing redundant handover (HO) has gained more importance after the existence ... more The challenge of removing redundant handover (HO) has gained more importance after the existence and deployment of femtocell in the network. By nature, the existence of femtocell can lead to the increase of handover initiation. However, 3GPP standard provides Mobility Robustness Optimization (MRO) to optimize handover performance. MRO is a use-case for Self-Organizing Network (SON). The conventional MRO algorithm tunes handover parameters based on counts of handover failures and handover events. In addition, conventional MRO algorithm uses hysteresis only to adjust and improve HO performance. In this paper, we propose an improved MRO algorithm by taking into account new optimization parameters, which is Time To Trigger parameter (TTT) to improve MRO algorithm performance in terms of reducing Ping-Pong rate and lower HO failure rate between femtocell and macrocell. We compared our improved MRO algorithm with the conventional one. The simulation results show remarkable improvement of the improved MRO algorithm over the standard one.
The Journal of Steroid Biochemistry and Molecular Biology, 1991
Stimulation of incubated rat adrenal slices with ACTH(I-24) resulted in an increase in the releas... more Stimulation of incubated rat adrenal slices with ACTH(I-24) resulted in an increase in the release of both corticosterone and specific corticosterone-binding protein into the incubation medium. The release of corticosterone and binding protein was dose and calcium dependent with adrenals from animals pretreated with betamethasone. While the secretion of corticosterone was continuous throughout the incubation period, there appeared to be a limit to the increase in binding capacity. The specificity of steroid binding to the adrenal protein showed a similar profile to that of corticosteroid-binding globulin (CBG) in rat serum. A Western blot analysis using anti-rat CBG as the primary antiserum, showed that the adrenal protein was not CBG. [3H]corticosterone binding with disc electrophoresis, run at 2°C, gave a single peak with approximately the same Rf value for rat serum, purified CBG, and adrenal incubate; at 22°C peaks were only seen for rat serum or purified CBG. The data presented provides further evidence for the existence of a specific corticosterone-binding protein of adrenal origin released in conjunction with corticosterone. The adrenal protein would appear to have a lower affinity for corticosterone than does CBG, and to be functionally more labile. It is possible that the adrenal protein may be CBG that has been internalized, modified and released with corticosterone.
In this 28-day, randomised, double-blind, placebo-controlled trial, 100 adults with self-reported... more In this 28-day, randomised, double-blind, placebo-controlled trial, 100 adults with self-reported poor sleep received either a placebo or a standardised Bacopa monnieri extract (150 mg twice daily). Outcome measures included the Bergen Insomnia Scale (primary outcome measure), Functional Outcomes of Sleep Questionnaire, Pittsburgh Sleep Diary, Short Form-36 Health Survey, and the Depression, Anxiety, and Stress Scale. Changes in salivary concentrations of cortisol, dehydroepiandrosterone sulfate, immunoglobulin A (sIgA), α-amylase (sAA), C-reactive protein, melatonin, and the fatigue biomarker index were also assessed. Based on the Bergen Insomnia Scale, Bacopa monnieri did not improve sleep patterns more than the placebo; however, it was associated with greater improvements in emotional wellbeing, general health, and pain-related symptoms. Bacopa monnieri was also associated with greater reductions in sIgA and sAA compared to the placebo. Future clinical trials using varying doses,...
Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2006
International Journal of Agriculture and Biology, 2014
Whole body and water-borne cortisol levels were measured in captive reared and wild Rainbowfish (... more Whole body and water-borne cortisol levels were measured in captive reared and wild Rainbowfish (Melanoteania duboulayi Castelnau 1878) subjected to social isolation by confining them in a beaker for 30 min to induce an acute stress response. Wild fish had higher levels of cortisol before and after exposure to a mild stressor and also showed the greatest stress response. The differences in stress responses are likely the result of artificial selection in the captive environment. Importantly, there was a strong linear relationship between whole body and water-borne cortisol in wild and captive reared populations (r 2 =0. 95 and 0.84, respectively) suggesting that noninvasive assays for cortisol provide a valuable alternative for whole body cortisol levels in small fishes. © 2014 Friends Science Publishers
Brain, behavior, and immunity, 2006
Exposure to endotoxin during the neonatal period in the rat has been shown to alter the developme... more Exposure to endotoxin during the neonatal period in the rat has been shown to alter the development of the hypothalamic-pituitary-adrenal axis, inducing hyper-responsivity and increased glucocorticoid production in later-life. Glucocorticoids are known to have major metabolic effects, therefore, early life endotoxin exposure may have potentially serious consequences for metabolic homeostasis in the exposed animal. The aims of this study were therefore to assess the effect of neonatal bacterial endotoxin exposure on subsequent glucose homeostasis, insulin action and corticosterone production from puberty through to senescence. Male Fischer-344 rat pups were treated with bacterial endotoxin (0.05 mg/kg Salmonella enteritidis i.p.) or vehicle (sterile pyrogen free saline) on days 3 and 5 postnatally. Insulin and glucose levels were assessed before and during and intraperitoneal glucose tolerance test (IPGTT) together with body mass on postnatal days 40, 80, and 400. In addition, circul...
The Journal of steroid biochemistry and molecular biology, 2006
Corticosteroid-binding globulin (CBG) is a plasma glycoprotein that is primarily synthesized in t... more Corticosteroid-binding globulin (CBG) is a plasma glycoprotein that is primarily synthesized in the liver and binds cortisol and progesterone with high affinity. In this study, a CBG secreting hepatocellular carcinoma derived cell line (HepG2) was used to investigate the hormonal regulation of hepatic CBG synthesis. HepG2 cells were grown for 72 h in 30, 300 and 3000 nM concentrations of estradiol (E2), testosterone (T), insulin, thyroxin (T4) and dexamethasone (DMZ) and the secreted CBG quantified by a novel enzyme-linked immunosorbent assay (ELISA). Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) was carried out to determine the effects of these hormones on the relative distribution of CBG glycoforms. Insulin, T4 and high concentrations of E2 decreased the secretion of CBG by HepG2 cells (p<0.05). Ethanol, the solvent used for E2, T and DMZ, also significantly attenuated CBG secretion. 2D-PAGE resolved 13-14 glycoforms of CBG produced by HepG2 cells. Insulin caused...
Steroids, 1995
The glycoprotein corticosteroid-binding globulin (CBG) migrates as doublet bands in PAGE and SDS-... more The glycoprotein corticosteroid-binding globulin (CBG) migrates as doublet bands in PAGE and SDS-PAGE, and as numerous bands in isoelectric focusing (IEF). This study deals with the origin of this heterogeneity. Desialation of rat CBG with neuraminidase does not abolish the doublet in either PAGE or SDS-PAGE, indicating that the doublet does not arise as a result of differences in sialic
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 2006
There is an emerging interest in utilizing local and systemic administration of bisphosphonates i... more There is an emerging interest in utilizing local and systemic administration of bisphosphonates in orthopedics. The primary objective of this study was to use (99m)Tc-pamidronate ((99m)Tc-PAM) as a tool and compare bone and tissue uptake by local versus systemic administration. (99m)Tc-PAM was administered intravenously (i.v.), subcutaneously (s.c.) and by direct application (d.a.) on a surgically exposed and fractured femur (d.a.#f). The animals were imaged at 2 h and 24 h after administration and then killed. Organs were harvested, and their radioactivity was estimated. Specific uptake in the right femur was compared between groups, as was systemic exposure to (99m)Tc PAM. Bone uptake of (99m)Tc-PAM in the i.v. and s.c. groups was 2.2 +/- 0.15 and 0.65 +/- 0.07% ID/g, respectively, at the 2 h time point. Uptake by surgically exposed right femur (d.a) was 5.15 +/- 0.26% ID/g, 134% higher than the femoral uptake by the i.v. method (P < 0.05). In the presence of exposed bone when ...
International Conference on Spinal Manipulation, 2002
2 page(s
PROTEOMICS, 2012
Human sex hormone binding globulin (hSHBG) is a serum glycoprotein central to the transport and t... more Human sex hormone binding globulin (hSHBG) is a serum glycoprotein central to the transport and targeted delivery of sex hormones to steroid-sensitive tissues. Several molecular mechanisms of action of hSHBG, including the function of its attached glycans remain unknown. Here, we perform a detailed site-specific characterization of the N- and O-linked glycosylation of serum-derived hSHBG. MS-driven glycoproteomics and glycomics combined with exoglycosidase treatment were used in a bottom-up and top-down manner to determine glycosylation sites, site-specific occupancies and monosaccharide compositions, detailed glycan structures, and the higher level arrangement of glycans on intact hSHBG. It was found that serum-derived hSHBG is N-glycosylated at Asn(351) and Asn(367) with average molar occupancies of 85.1 and 95.3%, respectively. Both sites are occupied by the same six sialylated and partly core fucosylated bi- and triantennary N-Glycoforms with lactosamine-type antennas of the form (±NeuAcα6)Galβ4GlcNAc. N-Glycoforms of Asn(367) were slightly more branched and core fucosylated than Asn(351) N-glycoforms due probably to a more surface-exposed glycosylation site. The N-terminal Thr(7) was fully occupied by the two O-linked glycans NeuAcα3Galβ3(NeuAcα6)GalNAc (where NeuAc is N-acetylneuraminic acid and GalNAc is N-acetylgalactosamine) and NeuAcα3Galβ3GalNAc in a 1:6 molar ratio. Electrophoretic analysis of intact hSHBG revealed size and charge heterogeneity of the isoforms circulating in blood serum. Interestingly, the size and charge heterogeneity were shown to originate predominantly from differential Asn(351) glycan occupancies and N-glycan sialylation that may modulate the hSHBG activity. To date, this work represents the most detailed structural map of the heterogeneous hSHBG glycosylation, which is a prerequisite for investigating the functional aspects of the hSHBG glycans.
Molecular & Cellular Proteomics, 2011
Human corticosteroid-binding globulin (CBG), a heavily glycosylated protein containing six N-link... more Human corticosteroid-binding globulin (CBG), a heavily glycosylated protein containing six N-linked glycosylation sites, transports cortisol and other corticosteroids in blood circulation. Here, we investigate the biological importance of the N-glycans of CBG derived from human serum by performing a structural and functional characterization of CBG N-glycosylation. Liquid chromatography-tandem MS-based glycoproteomics and glycomics combined with exoglycosidase treatment revealed 26 complex type N-glycoforms, all of which were terminated with ␣2,3-linked neuraminic acid (NeuAc) residues. The CBG N-glycans showed predominantly bi-and tri-antennary branching, but higher branching was also observed. N-glycans from all six N-glycosylation sites were identified with high site occupancies (70.5-99.5%) and glycoforms from all sites contained a relatively low degree of core-fucosylation (0-34.9%). CBG showed site-specific glycosylation and the site-to-site differences in core-fucosylation and branching could be in silico correlated with the accessibility to the individual glycosylation sites on the maturely folded protein. Deglycosylated and desialylated CBG analogs were generated to investigate the biological importance of CBG N-glycans. As a functional assay, MCF-7 cells were challenged with native and glycan-modified CBG and the amount of cAMP, which is produced as a quantitative response upon CBG binding to its cell surface receptor, was used to evaluate the CBG:receptor interaction. The removal of both CBG N-glycans and NeuAc residues increased the production of cAMP significantly. This confirms that N-glycans are involved in the CBG:receptor interaction and indicates that the modulation is performed by steric and/or electrostatic means through the terminal NeuAc residues.
Memory (Hove, England), Oct 23, 2015
For eyewitness testimony to be considered reliable, it is important to ensure memory remains accu... more For eyewitness testimony to be considered reliable, it is important to ensure memory remains accurate following the event. As many testimonies involve traumatic, as opposed to neutral, events, it is important to consider the role of distress in susceptibility to false memories. The aim of this study was to investigate whether cortisol response following a stressor would be associated with susceptibility to false memories. Psychological distress responses were also investigated, specifically, dissociation, intrusions, and avoidance. Participants were allocated to one of three conditions: those who viewed a neutral film (N = 35), those who viewed a real trauma film (N = 35), and a trauma "reappraisal" group where participants were told the film was not real (N = 35). All received misinformation about the film in the form of a narrative. Participants provided saliva samples (to assess cortisol) and completed distress and memory questionnaires. Cortisol response was a signific...
2014 IEEE International Conference on Control System, Computing and Engineering (ICCSCE 2014), 2014
The challenge of removing redundant handover (HO) has gained more importance after the existence ... more The challenge of removing redundant handover (HO) has gained more importance after the existence and deployment of femtocell in the network. By nature, the existence of femtocell can lead to the increase of handover initiation. However, 3GPP standard provides Mobility Robustness Optimization (MRO) to optimize handover performance. MRO is a use-case for Self-Organizing Network (SON). The conventional MRO algorithm tunes handover parameters based on counts of handover failures and handover events. In addition, conventional MRO algorithm uses hysteresis only to adjust and improve HO performance. In this paper, we propose an improved MRO algorithm by taking into account new optimization parameters, which is Time To Trigger parameter (TTT) to improve MRO algorithm performance in terms of reducing Ping-Pong rate and lower HO failure rate between femtocell and macrocell. We compared our improved MRO algorithm with the conventional one. The simulation results show remarkable improvement of the improved MRO algorithm over the standard one.
The Journal of Steroid Biochemistry and Molecular Biology, 1991
Stimulation of incubated rat adrenal slices with ACTH(I-24) resulted in an increase in the releas... more Stimulation of incubated rat adrenal slices with ACTH(I-24) resulted in an increase in the release of both corticosterone and specific corticosterone-binding protein into the incubation medium. The release of corticosterone and binding protein was dose and calcium dependent with adrenals from animals pretreated with betamethasone. While the secretion of corticosterone was continuous throughout the incubation period, there appeared to be a limit to the increase in binding capacity. The specificity of steroid binding to the adrenal protein showed a similar profile to that of corticosteroid-binding globulin (CBG) in rat serum. A Western blot analysis using anti-rat CBG as the primary antiserum, showed that the adrenal protein was not CBG. [3H]corticosterone binding with disc electrophoresis, run at 2°C, gave a single peak with approximately the same Rf value for rat serum, purified CBG, and adrenal incubate; at 22°C peaks were only seen for rat serum or purified CBG. The data presented provides further evidence for the existence of a specific corticosterone-binding protein of adrenal origin released in conjunction with corticosterone. The adrenal protein would appear to have a lower affinity for corticosterone than does CBG, and to be functionally more labile. It is possible that the adrenal protein may be CBG that has been internalized, modified and released with corticosterone.
In this 28-day, randomised, double-blind, placebo-controlled trial, 100 adults with self-reported... more In this 28-day, randomised, double-blind, placebo-controlled trial, 100 adults with self-reported poor sleep received either a placebo or a standardised Bacopa monnieri extract (150 mg twice daily). Outcome measures included the Bergen Insomnia Scale (primary outcome measure), Functional Outcomes of Sleep Questionnaire, Pittsburgh Sleep Diary, Short Form-36 Health Survey, and the Depression, Anxiety, and Stress Scale. Changes in salivary concentrations of cortisol, dehydroepiandrosterone sulfate, immunoglobulin A (sIgA), α-amylase (sAA), C-reactive protein, melatonin, and the fatigue biomarker index were also assessed. Based on the Bergen Insomnia Scale, Bacopa monnieri did not improve sleep patterns more than the placebo; however, it was associated with greater improvements in emotional wellbeing, general health, and pain-related symptoms. Bacopa monnieri was also associated with greater reductions in sIgA and sAA compared to the placebo. Future clinical trials using varying doses,...
Society of Nuclear Medicine Annual Meeting Abstracts, May 1, 2006
International Journal of Agriculture and Biology, 2014
Whole body and water-borne cortisol levels were measured in captive reared and wild Rainbowfish (... more Whole body and water-borne cortisol levels were measured in captive reared and wild Rainbowfish (Melanoteania duboulayi Castelnau 1878) subjected to social isolation by confining them in a beaker for 30 min to induce an acute stress response. Wild fish had higher levels of cortisol before and after exposure to a mild stressor and also showed the greatest stress response. The differences in stress responses are likely the result of artificial selection in the captive environment. Importantly, there was a strong linear relationship between whole body and water-borne cortisol in wild and captive reared populations (r 2 =0. 95 and 0.84, respectively) suggesting that noninvasive assays for cortisol provide a valuable alternative for whole body cortisol levels in small fishes. © 2014 Friends Science Publishers
Brain, behavior, and immunity, 2006
Exposure to endotoxin during the neonatal period in the rat has been shown to alter the developme... more Exposure to endotoxin during the neonatal period in the rat has been shown to alter the development of the hypothalamic-pituitary-adrenal axis, inducing hyper-responsivity and increased glucocorticoid production in later-life. Glucocorticoids are known to have major metabolic effects, therefore, early life endotoxin exposure may have potentially serious consequences for metabolic homeostasis in the exposed animal. The aims of this study were therefore to assess the effect of neonatal bacterial endotoxin exposure on subsequent glucose homeostasis, insulin action and corticosterone production from puberty through to senescence. Male Fischer-344 rat pups were treated with bacterial endotoxin (0.05 mg/kg Salmonella enteritidis i.p.) or vehicle (sterile pyrogen free saline) on days 3 and 5 postnatally. Insulin and glucose levels were assessed before and during and intraperitoneal glucose tolerance test (IPGTT) together with body mass on postnatal days 40, 80, and 400. In addition, circul...
The Journal of steroid biochemistry and molecular biology, 2006
Corticosteroid-binding globulin (CBG) is a plasma glycoprotein that is primarily synthesized in t... more Corticosteroid-binding globulin (CBG) is a plasma glycoprotein that is primarily synthesized in the liver and binds cortisol and progesterone with high affinity. In this study, a CBG secreting hepatocellular carcinoma derived cell line (HepG2) was used to investigate the hormonal regulation of hepatic CBG synthesis. HepG2 cells were grown for 72 h in 30, 300 and 3000 nM concentrations of estradiol (E2), testosterone (T), insulin, thyroxin (T4) and dexamethasone (DMZ) and the secreted CBG quantified by a novel enzyme-linked immunosorbent assay (ELISA). Two-dimensional polyacrylamide gel electrophoresis (2D-PAGE) was carried out to determine the effects of these hormones on the relative distribution of CBG glycoforms. Insulin, T4 and high concentrations of E2 decreased the secretion of CBG by HepG2 cells (p<0.05). Ethanol, the solvent used for E2, T and DMZ, also significantly attenuated CBG secretion. 2D-PAGE resolved 13-14 glycoforms of CBG produced by HepG2 cells. Insulin caused...
Steroids, 1995
The glycoprotein corticosteroid-binding globulin (CBG) migrates as doublet bands in PAGE and SDS-... more The glycoprotein corticosteroid-binding globulin (CBG) migrates as doublet bands in PAGE and SDS-PAGE, and as numerous bands in isoelectric focusing (IEF). This study deals with the origin of this heterogeneity. Desialation of rat CBG with neuraminidase does not abolish the doublet in either PAGE or SDS-PAGE, indicating that the doublet does not arise as a result of differences in sialic
Journal of orthopaedic science : official journal of the Japanese Orthopaedic Association, 2006
There is an emerging interest in utilizing local and systemic administration of bisphosphonates i... more There is an emerging interest in utilizing local and systemic administration of bisphosphonates in orthopedics. The primary objective of this study was to use (99m)Tc-pamidronate ((99m)Tc-PAM) as a tool and compare bone and tissue uptake by local versus systemic administration. (99m)Tc-PAM was administered intravenously (i.v.), subcutaneously (s.c.) and by direct application (d.a.) on a surgically exposed and fractured femur (d.a.#f). The animals were imaged at 2 h and 24 h after administration and then killed. Organs were harvested, and their radioactivity was estimated. Specific uptake in the right femur was compared between groups, as was systemic exposure to (99m)Tc PAM. Bone uptake of (99m)Tc-PAM in the i.v. and s.c. groups was 2.2 +/- 0.15 and 0.65 +/- 0.07% ID/g, respectively, at the 2 h time point. Uptake by surgically exposed right femur (d.a) was 5.15 +/- 0.26% ID/g, 134% higher than the femoral uptake by the i.v. method (P < 0.05). In the presence of exposed bone when ...