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Publication
Journal: International Journal of Sports Medicine
September/10/2015
Abstract
Currently it is unclear whether blood flow (BF) or muscle oxidative capacity best governs performance during intermittent contractions to failure. The aim of this study was to determine oxygenation kinetics and BF responses during intermittent (10 s contraction: 3 s release) contractions at 40% of MVC in rock climbers of different ability (N=38). Total forearm BF, as well as de-oxygenation and re-oxygenation of the flexor digitorum profundus (FDP) and the flexor carpi radialis (FCR) were assessed. Compared to the control, intermediate and advanced groups, the elite climbers had a significantly (p<0.05) greater force time integral (FTI), MVC and MVC/kg. Furthermore, the elite climbers de-oxygenated the FDP significantly more during the first (7.8, 11.9, 12.4 vs. 15.7 O2%) and middle (7.3, 8.8, 10.4 vs.15.3 O2%) phases of contractions as well as for the FCR during the first phase only (8.3, 7, 11.7 vs. 13.3 O2%). They also had a significantly higher BF upon release of the contractions (656, 701, 764 vs. 971 mL ∙ min(-1)). The higher FTI seen in elite climbers may be attributable to a greater blood delivery, and an enhanced O2 recovery during the 3 s release periods, as well as a superior muscle oxidative capacity associated with the greater de-oxygenation during the 10 s contractions.
Publication
Journal: Annual International Conference of the IEEE Engineering in Medicine and Biology - Proceedings
March/28/2011
Abstract
This paper reports a method that aims to quantify the changes of tumour vascular structure as a result of drug treatment. The measures we have investigated to date include: vessel radii, inter-branch lengths, tortuosity and branch angles. We show that the distribution of vessel radii is better modelled as a gamma distribution as opposed to the log-normal distribution asserted by other researchers. We propose a new metric based on multiple linear regression to measure vascular tortuosity. We report statistical analyses which confirm that (as expected), at different significance levels, all the drugs we have tested (FTI, Iressa, Nelfinavir and PI-103) have positive effects in improving a tumour's vascular network. In each case, the changes are quantified.
Publication
Journal: PeerJ
November/13/2018
Abstract
UNASSIGNED
The table tennis serve involves complex spatial movements combined with biomechanial characteristics. Although the differences in lower-limb biomechanial characteristics to a great extent influence the translational and spinning velocity of the ball when using the different styles of table tennis serve, few researchers have studied their mechanics. Therefore, the aim of this study was to investigate the differences in lower-limb activity between the squat and standing serves during a table tennis short serve.
UNASSIGNED
Ten advanced female table tennis participants performed a squat serve and standing serve in random order. A Vicon motion analysis system and a Novel Pedar insole plantar pressure measurement system were used to record kinematics and kinetics data, respectively.
UNASSIGNED
Key findings from the study were that the squat serve not only showed significantly larger hip and knee flexion, as well as ankle dorsiflexion, it also showed significantly larger hip adduction and external knee rotation, with larger changing angular rate of the lower limb joints in the sagittal and the transverse planes when the two serving styles were compared. In addition, the force-time integral (FTI) was higher in the rear foot area for the standing serve.
UNASSIGNED
The results demonstrated that the squat serve needs higher lower limb drive during a table tennis short serve compared with a standing serve. These biomechanical considerations may be beneficial for table tennis athletes and coaches as a method of optimizing performance characteristics during both competition and training.
Publication
Journal: Optics Express
October/1/2012
Abstract
Fourier-Transform Imaging Spectroscopy (FTIS) has recently become a widely used tool for spectral imaging of biological fluorescent samples. Here we report on a novel double-pass FTIS system, that is capable of obtaining an excitation as well as an emission spectrum of the fluorescent sample with only a single sweep of the interferometer. This is achieved by modifying an existing FTIS system, placing the excitation source before the interferometer so as to spectrally modulate the excitation as well as the detection. An analysis of the acquired signal allows for the reconstruction of the excitation as well as the emission spectrum of each fluorophore assuming an independence of the two spectra for each fluorophore. Due to the patterned excitation generated by the Sagnac interferometer a substantial degree of optically sectioning is achieved at excitation wavelengths. Further analysis of the acquired data also enables the generation of optically sectioned emission images. A theoretical analysis and experimental data based on fluorescent beads are presented.
Publication
Journal: Journal of Surgical Research
August/29/2001
Abstract
Src is an oncoprotein which has been implicated in a number of human malignancies in which it has been shown to be overexpressed and highly activated. The precise mechanism of Src transformation, however, is still poorly understood. We hypothesized that Ras and other farnesylated proteins may mediate Src transformation. To test this hypothesis, v-Src-transfected rat fibroblasts (3Y1) were treated every 72 h with a 15 microM concentration of a farnesyl-transferase inhibitor (FTI). At 2 weeks, a focus formation assay was performed to assess transformation potential. Untreated and FTI-treated v-Src-transfected 3Y1 cells formed a mean of 39 (+/-2.6) and 29.8 (+/-2.9) foci per well, respectively. This 24% decrease was judged to be statistically significant (P = 0.02). Moreover, foci (>90%) in the FTI-treated wells were also consistently smaller than foci in the untreated wells. Western blots with antibody directed toward H-Ras confirmed complete inhibition of Ras farnesylation in the treated cell lines. The specificity of this inhibition was verified by Western blot using antibody specific for Rap1A. The transforming potential of v-Src is inhibited, but not eliminated by FTI treatment. This suggests that v-Src transformation is mediated in part by farnesylated proteins, one of which may be Ras.
Publication
Journal: Schweizerische medizinische Wochenschrift
January/24/1977
Abstract
Serum-T4, -T3, FTI, basal TSH and TRH-induced TSH response were measured in 80 patients with simple nontoxic goiter and in 24 patients with nontoxic recurrent goiter in a surgical unit. 55 of the 80 patients with simple goiter and 11 patients with recurrent goiter had normal individual TSH values. Mean FTI and serum T3 were not statistically different from age and sex related normal values, except serum-T3, which was above normal in elderly goiter patients. The incidence of elevated TSH reserve (preclinical hypothyroidism) was significantly higher (p less than 0.0005) in recurrent than in simple goiter (10 of 24 vs. 8 of 80 patients). Simple goiter aptients with preclinical hypothyroidism had a lower-than-normal mean serum T4 level, whereas mean serum T4 and T3 concentrations were higher than normal in preclinically hypothyroid recurrent goiter patients. In these subjects raised TSH values and goitrogenesis possibly may be related to lower sensitivity of the pituitary to thyroid hormones. 17 simple goiter patients and 3 recurrent goiter patients with normal circulating serum T4 and T3 levels showed no response to TSH to TRH. This suprising finding is related to preclinical hyperthyroidism on the basis of autonomously functioning thyroid compartments. In 12 tested patients TRH responsiveness recovered following goiter resection. The mean T3 response to TRH in goiter patients with normal or elevated TSH reserve was subnormal. This indicates that thyroid reserve is potentially decreased even in goiter patients whose thyroid function was, on the evidence of normal TSH values, actually appropriate.
Publication
Journal: Neuroscience Letters
November/25/2014
Abstract
Isoprenylation is crucial step for activating many intracellular signaling. The present study examined whether inhibition of the protein isoprenylation could affect neuropathic pain in partial sciatic nerve-ligated mice. Intrathecal treatment with a geranylgeranyl transferase I inhibitor GGTI-2133, but not with a farnesyl transferase inhibitor FTI-277, dose-dependently blocked the thermal hyperalgesia in partial sciatic nerve-ligated mice. Intrathecal treatment with GGTI-2133 also attenuated the mechanical allodynia in partial sciatic nerve-ligated mice. Phosphorylated MARCKS expression was increased in the ipsilateral side of the spinal cord dorsal horn in partial sciatic nerve-ligated mice, and this increase was attenuated by GGTI-2133 but not by FTI-277. These results suggest that protein isoprenylation by geranylgeranyl transferase I is involved in the neuropathic pain.
Publication
Journal: Pakistan Journal of Medical Sciences
December/18/2013
Abstract
OBJECTIVE
The aim of this study was to investigate thyroid function tests in Gestational Diabetes Mellitus (GDM) and pre-gestational DM and control group. Methodology : There were 61 pregnant diabetic women in study group and 35 pregnant women in control group. Serum T4, T3, T3RU, FTI, TSH and Anti TPO Ab were assessed in each person. Results : About 36% of patients had GDM and 64% pre-gestational DM. Thyroid dysfunction was detected in 18% of study group compared with 8.6% of control group (P = 0.2). There was Thyroid dysfunction in 4.5% of GDM and 25.6% of pregestational DM (P = 0.045). There was no statistically significant difference between thyroid dysfunction in GDM group and control group (P=0.99).27% of GDM and 36% of pregestational DM and 23% of control group had positive titer of Anti TPO Ab without statistically significant differences among the three groups. Conclusion : Thyroid dysfunction is prevalent in women with pre-gestational DM so, thyroid function should be evaluated in these patients during pregnancy. Rate of thyroid dysfunction in GDM patients is similar to normal pregnant control women. High prevalence of positive titer of TPO Ab was seen in diabetic and non-diabetic pregnant women.
Publication
Journal: International Immunopharmacology
January/6/2004
Abstract
Farnesyltransferase inhibitors (FTIs) are anticancer compounds that inhibit Ras GTPases. Since Ras GTPases play key roles in T cell activation and function, we hypothesized that FTIs have immunomodulatory properties and are potential antirejection agents. An investigation was performed on a potent FTI to evaluate this hypothesis in the in vitro setting. The in vitro effects of the FTI A-228839 were evaluated. Lectin- or antigen presenting cell (APC)-induced lymphocyte proliferation in the presence of A-228839 was measured. The effects of A-228839 on 1E5 T cell polarity were assessed by microscopy. Intracellular calcium ([Ca(2+)](i)) kinetics of lectin-activated lymphocytes was monitored by flow cytometry. The effects of A-228839 on peripheral blood mononuclear cell (PBMC) cytokine production was assessed by a cytometric bead array method. Activation-induced apoptosis was measured with an annexin V staining assay.A-228839 inhibited lectin-induced proliferation (IC(50)=0.24+/-0.11 microM). The inhibitory effects of A-228839 on lectin induced lymphocyte proliferation were additive to those of CsA. A-228839 was more effective in inhibiting APC-induced T cell proliferation (IC(50)=0.10+/-0.09 microM). A-228839 significantly disrupted the polarized shape of 1E5 T cells at physiologic concentrations. A-228839 altered PBMC baseline [Ca(2+)](i) but did not affect [Ca(2+)](i) kinetics during lectin-induced lymphocyte activation. A-228839 inhibited lymphocyte Th1 cytokine production at submicromolar levels and promoted apoptosis in lectin-activated lymphocytes.A-228839 potently inhibits lymphocyte activation and function. Our results suggest that FTIs may represent a new class of clinically useful immunomodulatory agents. A-228839 has potent in vitro immunomodulatory properties that warrant in vivo evaluation as an antirejection agent.
Publication
Journal: International journal of fertility and women's medicine
July/18/2001
Abstract
OBJECTIVE
The purpose of this study was to evaluate thyroid function and TSH and cortisol (F) secretion in hyperandrogenemic women with nonclassical congenital adrenal hyperplasia (NC-CAH) due to 21-hydroxylase deficiency (Group A) when compared with women with hyperandrogenemic symptoms (menstrual irregularities, hirsutism, acne, seborrhea and sterility) of other etiologies (Group B).
METHODS
Seventy-two women were subjected to stimulation of the adrenal cortex with i.v. ACTH administration in the early proliferative phase of the menstrual cycle. Basal plasma TSH, T3, T4, and FTI as well as basal and ACTH-stimulated plasma F and 17-hydroxyprogesterone levels were determined.
RESULTS
According to internationally accepted criteria and HLA haplotyping, we diagnosed 28 NC-CAH patients as well as affected heterozygotes of the disease. No significant difference was found in the plasma T3, T4, or FTI or F concentrations between the women of the two groups. On the contrary, plasma TSH levels were significantly lower in patients with 21-hydroxylase deficiency when compared to the women with hyperandrogenemic symptoms of other etiologies.
CONCLUSIONS
The results of this study support a dysfunction of the hypothalamic-pituitary-thyroidal axis due to altered ACTH secretion patterns.
Publication
Journal: Frontiers in Pharmacology
November/13/2018
Abstract
Simvastatin (SV) enhances glutamate release and synaptic plasticity in hippocampal CA1 region upon activation of α7 nicotinic acetylcholine receptor (α7nAChR). In this study, we examined the effects of SV on the functional activity of α7nAChR on CA1 pyramidal cells using patch-clamp recording and explored the underlying mechanisms. We found that the treatment of hippocampal slices with SV for 2 h induced a dose-dependent increase in the amplitude of ACh-evoked inward currents (IACh) and the level of α7nAChR protein on the cell membrane without change in the level of α7nAChR phosphorylation. These SV-induced phenotypes were suppressed by addition of farnesol (FOH) that converts farnesyl pyrophosphate, but not geranylgeraniol. Similarly, the farnesyl transferase inhibitor FTIFTI. The SV-enhanced phosphorylation of PKC was sensitive to the IP3R antagonist 2-APB. The SV-increased amplitude of IACh was suppressed by PKC inhibitor GF109203X and Go6983, or CaMKII inhibitor KN93. The SV- and FTI-enhanced trafficking of α7nAChR was sensitive to KN93, but not GF109203X or Go6983. The PKC activator PMA increased α7nAChR activity, but had no effect on trafficking of α7nAChR. Collectively, these results indicate that acute treatment with SV enhances the activity and trafficking of α7nAChR by increasing PKC phosphorylation and reducing farnesyl-pyrophosphate to trigger NMDA receptor-mediated CaMKII activation.
Publication
Journal: Experimental Cell Research
December/10/2003
Abstract
Angiogenesis is regulated by growth factors which activate tyrosine kinase receptors leading to the activation of a number of intracellular signaling pathways. The specific function of H-Ras during FGF-2 stimulated endothelial cell differentiation, defined as invasive growth and formation of branching networks in fibrin gels, was investigated by using conditionally immortalized endothelial cell lines induced to express H-Ras mutants. Expression of inhibitory N17Ras did not impair differentiation in response to FGF-2 and TNF-alpha. The farnesyltransferase inhibitor FTI-277 inhibited farnesylation of Ras but did not inhibit differentiation of human microvascular endothelial cells or mouse brain endothelial cells. In contrast, activated V12Ras inhibited endothelial cell differentiation and cells displayed a transformed phenotype with an increased rate of proliferation and loss of contact inhibited growth. Furthermore, V12Ras expressing endothelial cells grew as solid tumors when injected subcutaneously into mice. Our data suggest that, in endothelial cells, H-Ras activity is not required for differentiation. However, this activity must be tightly regulated as aberrant activity can disturb the ability of endothelial cells to undergo differentiation.
Publication
Journal: Clinica Chimica Acta
March/5/2007
Abstract
BACKGROUND
Estimates of the free thyroxine concentration can be made using measurements of thyroxine (T4) and the thyroid hormone binding ratio (THBR, usually reported as T-uptake) according to the formula free thyroxine index (FTI)=T4xTHBR. We evaluated the performance characteristics of 7 pairs of automated T4 and T-uptake methods.
METHODS
We evaluated the Architect i2000, AxSYM, ADVIA Centaur, UniCel DxI 800, Immulite 2000, Modular E170 and Vitros ECi methods for T4 and T-uptake. Imprecision was assessed by duplicate determinations on 3 levels of quality control material per run, 2 runs per day, on 5 separate days. Method comparison studies were performed with 205 patient samples and 68 samples from subjects in the second or third trimester of pregnancy. Results for both imprecision and method comparison were converted to the THBR as outlined by each method's manufacturer.
RESULTS
Overall CVs for T4 and THBR methods were 3.2-8.9% and 1.2-6.7%, respectively. T4 methods generally agreed well. The THBR methods did not agree nearly as well. Comparison of FTI results with free T4 by equilibrium dialysis showed good correlation but different slopes.
CONCLUSIONS
All methods show adequate precision but the THBR and FTI results are not well standardized.
Publication
Journal: Heart and Vessels
August/5/1990
Abstract
We have proposed the systolic pressure-volume area (PVA) as a measure of the total mechanical energy generated by ventricular contraction, and we found a closely linear correlation between PVA and cardiac oxygen consumption (VO2). Although the force-time integral (FTI) has long been considered to be the most reliable correlate of cardiac oxygen consumption (VO2), we have already shown that VO2 remained constant although FTI was changed while PVA was kept constant in the excised, cross-circulated dog left ventricle. This means that PVA is superior to FTI as a predictor of VO2. In the present study, we studied whether a linear addition of FTI to PVA could improve the prediction of VO2 from PVA in isovolumic and ejecting contractions with different afterload pressures in the same type of dog left ventricle preparation. Although left ventricular VO2 was always closely correlated with either PVA (r = 0.967, mean after z-transformation) or FTI (mean r = 0.925), multiple regression analysis indicated that PVA alone accounted for as much as 94% (mean) of the variance of VO2 and that FTI linearly added to PVA accounted for an additional few percent of the variance (statistically significant in less than half the cases). We conclude that the addition of FTI to PVA does not improve the predictability of VO2 from PVA in ordinary contractions.
Publication
Journal: IEEE Transactions on Neural Systems and Rehabilitation Engineering
March/19/2003
Abstract
Stimulation patterns can be optimized by maximizing the force-time integral (FTI) per stimulation pulse of the elicited muscle contraction. Such patterns, providing the desired force output with the minimum number of pulses, may reduce muscle fatigue, which has been shown to correlate to the number of pulses delivered. Applications of electrical stimulation to use muscle as a controllable biological actuator may, therefore, be improved. Although muscle operates over a range of lengths, optimized patterns have been determined only at optimal muscle length. In this study, the patterns with up to four pulses that produced the highest isometric FTI were determined at 10 muscle lengths for 11 rabbit tibialis anterior muscles. The interpulse intervals (IPIs) used ranged from 4 to 54 ms. At high muscle length, the optimal stimulation pattern consisted of an initial short IPI (doublet) followed by longer IPIs, in agreement with previous studies. However, at low length, the third pulse still elicited more than linear summation (triplet); furthermore, the relative enhancement of the FTI per pulse was considerably larger at low length than at high length, suggesting that optimal stimulation patterns are length dependent.
Publication
Journal: Muscle and Nerve
July/8/2008
Abstract
It is essential to determine optimal parameters of stimulation to maintain muscle force during neuromuscular electrical stimulation (NMES). Protocols that increase in frequency and include doublets can prolong force output over time. However, stimulation intensity level could differentially affect muscle force output during variable-frequency NMES. We compared three intermittent stimulation patterns at maximal and submaximal intensities of stimulation of the median nerve: (1) a constant 20-HZ pattern; (2) 90 s at 20 HZ followed by a 90-s increase from 20 to 40 HZ; and (3) 90 s at 20 HZ followed by 90 s of doublets at 20 HZ. At submaximal intensities, the doublet pattern produced the highest overall force-time integral (FTI). At maximal intensities, the doublet pattern produced the lowest FTI and the increasing frequency pattern produced the least amount of fatigue. Thus, double-pulse stimulation was more effective during submaximal than maximal intensity NMES. These data demonstrate that intensity level must be taken into consideration when programming frequency patterns for NMES devices.
Publication
Journal: Applied Biochemistry and Biotechnology
December/16/2001
Abstract
This study deals with the bioconversion of xylose into xylitol by Candida guilliermondii FTI 20037 using eucalyptus hemicellulosic hydrolysate obtained by acid hydrolysis. The influence of various parameters (ammonium sulfate, rice bran, pH, and xylose concentration) on the production of xylitol was evaluated. The experiments were based on multivariate statistical concepts, with the application of factorial design techniques to identify the most important variables in the process. The levels of these variables were quantified by the response surface methodology, which permitted the establishment of a significant mathematical model with a coefficient determination of R2 = 0.92. The best results (xylitol = 10.0 g/L, yield factor = 0.2 g/g, and productivity = 0.1 g/[L x h]) were attained with hydrolysate containing ammonium sulfate (1.1 g/L), rice bran (5.0 g/L), and xylose (initial concentration of 60.0 g/L), after 72 h of fermentation. The pH of fermentation was adjusted to 8.0 and the inoculum level utilized was 3 g/L.
Publication
Journal: Cancer and Metastasis Reviews
November/23/1998
Abstract
ras is the oncogene most frequently found in human cancers, being detected in 30% of most human cancers and at significantly higher rates in certain cancers including pancreatic (90%) and colon (50%) [1]. Almost 10 years ago it was shown that a C-terminal lipid modification of Ras, catalyzed by a specific farnesyl-protein transferase (FPTase), was required for the function of both normal and oncogenic Ras proteins. This finding spurred the development of FPTase inhibitors (FTIs) as a potential cancer therapy directed at the ras oncogene. FTIs have exhibited potent antiproliferative activity in cell culture and animal tumor models with a surprising lack of toxicity to normal tissues. However, while FTIs were originally conceptualized as Ras-specific agents, their mechanism of action is significantly more complicated than originally envisioned.
Publication
Journal: Journal of Cardiovascular Electrophysiology
November/6/2017
Abstract
This study sought to investigate specific contact force (CF) parameters to guide cavotricuspid isthmus (CTI) ablation and compare the outcome with a historical control cohort.
Patients (30) undergoing CTI ablation were enrolled prospectively in the Study cohort and compared with a retrospective Control cohort of 30 patients. Ablation in the Study cohort was performed using CF parameters >10 g and <40 g and a Force Time Integral (FTI) of 800 ± 10 g. The Control cohort underwent traditionally guided CTI ablation. Traditional parameters (electrogram and impedance change) were assessed in both cohorts. All ablations regardless of achieving targets were included in data analysis. Bidirectional CTI block was achieved in all of the Study and 27 of the Control cohort. Atrial flutter recurred in 3 (10%) patients (follow-up 564 ± 212 days) in the study cohort and in 3 (10%) patients (follow-up 804 ± 540 days) in the Control cohort. There were no major complications in either cohort. Traditional parameters correlated poorly with CF parameters. In the Study cohort, flutter recurrence was associated with significantly lower FTI and ablation duration, but was not associated with total average CF.
CTI ablation can be safely performed using CF parameters guiding ablation, with similar long-term results to a historical ablation control group. Potentially CF parameters may provide adjunctive information to enable a more efficient CTI ablation. Further research is required to confirm this.
Publication
Journal: Acta Endocrinologica
March/10/1983
Abstract
Thyroid and pituitary function was studied in 10 male and 6 patients female during critical non-endocrine disease. Low concentrations of TT3 were observed in each case. Seven patients out of whom 3 survived, presented with low levels of TT4 due to deficiency in TBG in the presence of normal values of FTI and FT4, whereas a 'low T4-syndrome', characterized by low concentrations of both TT4 and FT4 was seen in 9 patients, 8 of whom died 1 to 16 days after evaluation of pituitary function. A diminished response of TSH to iv TRH (400 micrograms), as observed in 4 patients with normal FT4 and in all patients with 'low T4-syndrome', was not accompanied by a concomitant lack in stimulated release of LH, FSH and Pr1 in the majority of cases. However, the secretory maximum of LH and FSH following stimulation by LRH (100 micrograms iv) was delayed in 10 and in 9 patients, respectively, including patients both with normal and subnormal concentrations of FT4. From the above it appears that low stimulated concentrations of TSH in the presence of subnormal concentrations of FT4 indicate an extremely poor prognosis in critically ill patients. The abnormal behaviour of TSH in this group of patients cannot be explained by generalized pituitary insufficiency or by an increase in FT4.
Publication
Journal: Age and Ageing
September/21/1977
Abstract
A study of the well elderly living at home has demonstrated that the ranges for serum thyroxine (T4), triiodothyronine (T3) uptake and free-thyroxine index (FTI) are much narrower than those for the sick elderly in-patient. The prevalence of thyroid disease appears similar in both types of elderly population.
Publication
Journal: Acta Obstetricia et Gynecologica Scandinavica
May/12/2004
Abstract
BACKGROUND
The aim was to investigate the clinical, biochemical and ultrasonographic characteristics of Scandinavian women with polycystic ovarian syndrome (PCOS), and to see whether there were any differences between eumenorrhoic and oligoamenorrhoic women.
METHODS
Eighty women aged between 18 and 40 years with PCOS were investigated in a prospective study. The inclusion criteria were polycystic ovaries (PCO), body mass index (BMI) >25 kg/m(2) and at least one of the following: testosterone >2.5 nmol/L, sex hormone binding globulin (SHBG) <30 nmol/L, fasting C-peptide >1.0 nmol/L, oligoamenorrhea or hirsutism.
RESULTS
Eumenorrhoic and oligoamenorrhoic women with PCOS did not differ in age, age at menarche, blood pressure, BMI, free testosterone index (FTI), insulin C-peptide or fasting glucose. A thicker endometrium and a smaller ovarian volume were found in eumenorrhoic compared to oligoamenorrhoic patients. There was linear association between BMI and the number of diagnostic criteria met.
CONCLUSIONS
BMI was associated with the severity of the PCOS. There were no differences in basic clinical and biochemical parameters between eumenorrhoic and oligoamenorrhoic patients with PCOS.
Publication
Journal: Cancer Research
July/25/2004
Abstract
BMS-214662 and BMS-225975 are tetrahydrobenzodiazepine-based farnesyltransferase inhibitors (FTIs) that have nearly identical structures and very similar pharmacological profiles associated with farnesyltransferase (FT) inhibition. Despite their similar activity against FT in vitro and in cells, these compounds differ dramatically in their apoptotic potency and tumor-regressing activity in vivo. BMS-214662 is the most potent apoptotic FTI known and exhibits curative responses in mice bearing a variety of staged human tumor xenografts such as HCT-116 human colon tumor. By contrast, BMS-225975 does not cause tumor regression and at best causes partial tumor growth inhibition in staged HCT-116 human colon tumor xenografts. Lack of tumor regression activity in BMS-225975 was attributable to its relatively weak apoptotic potency, not to poor cell permeability or pharmacokinetics. Both compounds were equally effective in inhibiting Ras processing and causing accumulation of a variety of nonfarnesylated substrates of FT in HCT-116 cells. Because BMS-225975 has poor apoptotic activity compared with BMS-214662 but inhibits FT to the same extent as BMS-214662, it is very unlikely that FT inhibition alone can account for the apoptotic potency of BMS-214662. Clearly distinct patterns of sensitivities in a cell line panel were obtained for the apoptotic FTI BMS-214662 and the cytostatic FTI BMS-225975. Activation of the c-Jun-NH(2)-terminal kinase pathway was readily observed with BMS-214662 but not with BMS-225975. We developed a highly sensitive San-1 murine xenograft tumor model that is particularly useful for evaluating the in vivo activity of cytostatic FTIs such as BMS-225975.
Publication
Journal: Echocardiography
March/24/2011
Abstract
OBJECTIVE
To evaluate the accuracy of a semiautomatic quantification of left ventricular (LV) volumes and ejection fraction (EF) using two-dimensional (2D) feature tracking imaging (FTI).
METHODS
Thirty-four consecutive subjects (11 patients with dilated cardiomyopathy, 13 with hypertrophic cardiomyopathy, and 10 subjects with no cardiac disease) underwent, on the same day, trans-thoracic echocardiography (TTE) examination, FTI, and cardiac magnetic resonance imaging (MRI), as gold standard, in order to quantify LV volumes and EF. The echocardiographic quantification of LV volumes and EF was determined from four- and two-chamber views using both standard TTE Biplane Simpson's method and a semiautomatic border detection based on FTI. Furthermore, the time for data analysis for each method was measured.
RESULTS
The time required for semiautomatic analysis of volumes and EF was significantly lower (P < 0.0001) by FTI (71 seconds) in comparison with standard biplane Simpson's method (93 seconds). LV volumes obtained by FTI were significant underestimated (P < 0.001) in comparison with MRI. Bland-Altman analysis of EDV and ESV using FTI and cardiac MRI showed a low level of agreement for EDV (mean difference = 40.8; SD = 39) and ESV (mean difference = 38.1; SD = 42). On the contrary, no significant difference between FTI and MRI in assessing the LVEF was found; furthermore, a very low bias (2 ± 12) by Bland-Altman analysis was found between FTI and cardiac MRI for the quantification of EF.
CONCLUSIONS
Semiautomatic quantification of LV volumes using FTI allows an accurate, rapid, easy and reliable assessment of LV EF and a rough estimation of LV volumes.
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