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1.
J Obstet Gynaecol ; 39(6): 833-839, 2019 Aug.
Article in English | MEDLINE | ID: mdl-31006301

ABSTRACT

The objective of this prospective cohort study was to evaluate the therapeutic efficacy and safety of ultrasound-guided high-intensity focussed ultrasound (HIFU) in the treatment of uterine fibroids. Twenty premenopausal women with symptomatic fibroids underwent ultrasound-guided HIFU therapy. Twenty-two fibroids with a median baseline volume of 127.0 cm3 (range 18.5-481.2 cm3) were treated. The percentages fibroid volume reduction were 46.9 (range -8.8-73.1) at 1-month, 57.4 (-51.5-95.2) at 3-month, 60.1 (-18.9-97.8) at 6-month and 75.9 (-33.7-99.3) at 12-month, after treatment. The modified Uterine Fibroid Symptom and Quality of Life (UFS-QOL) scores were reduced by 40.7% (0-59.3%) at 3-month, 45.5% (0-70.4%) at 6-month and 44.9% (0-71.4%) at 12-month after treatment. Three patients required subsequent surgical interventions. No significant complications were encountered. Ultrasound-guided HIFU appears to be effective and safe for the treatment of symptomatic uterine fibroids in selected patients. Impact statement What is already known on this subject? Ultrasound-guided high-intensity focussed ultrasound (HIFU) is a relatively new uterine-sparing treatment for fibroids. Most clinical reports are from China, which suggest that this treatment is a safe and effective modality. However, in many other countries, HIFU treatment for fibroids, especially using ultrasound as image guidance, is still considered novel with limited clinical experience. What do the results of this study add? This preliminary report adds to our limited local experience on HIFU and provides reassurance on our continual utilisation of this treatment modality for fibroids. With the increasing demand of uterine-sparing alternatives, experiences shared among different countries are important to make this treatment modality generalisable and universally acceptable. What are the implications of these findings for clinical practice and/or further research?Ultrasound-guided HIFU (USgHIFU) can potential be offered as an alternative treatment modality for women with fibroids.


Subject(s)
High-Intensity Focused Ultrasound Ablation/methods , Leiomyoma/surgery , Uterine Neoplasms/surgery , Adult , Cohort Studies , Female , Humans , Leiomyoma/pathology , Middle Aged , Premenopause , Prospective Studies , Treatment Outcome , Ultrasonography , Uterine Neoplasms/pathology
2.
J Obstet Gynaecol Can ; 38(4): 357-61, 2016 Apr.
Article in English | MEDLINE | ID: mdl-27208605

ABSTRACT

OBJECTIVE: To determine the effect on ovarian reserve of ultrasound-guided high-intensity focused ultrasound (HIFU) in the treatment of uterine fibroids. METHODS: We performed a mid-study analysis of markers of ovarian reserve using data from a prospective cohort study evaluating the safety of ultrasound-guided HIFU for uterine fibroids. Blood samples obtained from 12 women with uterine fibroids less than one week before treatment were used for measurement of serum anti-Mullerian hormone (AMH), and this testing was repeated in the first, third, sixth, and 12th month after ultrasound-guided HIFU treatment. RESULTS: Fourteen fibroids from 12 patients were treated using ultrasound-guided HIFU. The median baseline fibroid volume was 101.2 cm(3) (range 18.5 to 349.2 cm(3)). The median treatment time was 140.5 minutes (46 to 192 minutes), and median sonication time was 1449 seconds (range 541 to 2445 seconds). The median energy delivered was 575 521.5 joules (range 216 400 to 898 273 joules). The median AMH levels (ng/mL) before treatment and at one, three, six, and 12 months after treatment were 0.3 (range 0.01 to 1.94), 0.47 (0.01 to 1.43), 0.205 (0.01 to 1.81), 0.26 (0 to 2.37), and 0.06 (0.02 to 1.04), respectively. There was no significant difference between the AMH levels before and at any time after treatment. No patient became amenorrheic or reported symptoms suggestive of menopause after treatment. CONCLUSION: Our preliminary experience suggests that ovarian reserve does not seem to be affected by ultrasound-guided HIFU in the treatment of uterine fibroids.


Subject(s)
High-Intensity Focused Ultrasound Ablation/instrumentation , High-Intensity Focused Ultrasound Ablation/methods , Leiomyoma/surgery , Ovarian Reserve , Uterine Neoplasms/surgery , Adult , Equipment Design , Female , Follow-Up Studies , Humans , Middle Aged , Prospective Studies
3.
Langmuir ; 30(8): 2206-15, 2014 Mar 04.
Article in English | MEDLINE | ID: mdl-24528207

ABSTRACT

We present the results of a systematic study on the porosity of silica microparticles and nanowires prepared by glancing angle deposition-metal-assisted chemical etching (GLAD-MACE) and interference lithography-metal-assisted chemical etching (IL-MACE) techniques using the thermoporometry (TPM) method. Good agreement was obtained between our TPM results and published data provided by the suppliers of silica microparticles. TPM characterization of the GLAD-MACE and IL-MACE nanowires was carried out on the basis of parameters obtained from TPM experiments on microparticles. Our nanowires showed a similar trend but lower values of the pore volume and surface area than nanowires prepared by MACE with AgNO3 solution. We attribute the enhanced bioanalysis performance of the GLAD-MACE nanowires based devices to the increased pore volume and total surface area of the nanowires.


Subject(s)
Nanowires/chemistry , Silicon Dioxide/chemistry , Silver Nitrate/chemistry , Nanowires/ultrastructure , Surface Properties
4.
Phys Chem Chem Phys ; 16(26): 13402-8, 2014 Jul 14.
Article in English | MEDLINE | ID: mdl-24879451

ABSTRACT

The fabrication of orderly arrays of free-standing, curved Si nanowires over large areas (1 cm × 1 cm) was demonstrated by means of interference lithography and intentional mechanical failure of a perforated Au catalyst during metal assisted chemical etching. Photoresist microgrooves were deposited on the perforated Au film to cause uneven etching which resulted in the build-up of bending stresses in the Au film to the point of catastrophic failure. By considering the initial positions of the holes in the perforated Au film relative to the photoresist constraints, the precise location of the fracture can be predicted using simple beam mechanics. Therefore, the type of curved nanowires obtained can be designed with a high degree of reliability and control. Four distinct types of nanowire arrangements were demonstrated for this study.

5.
J Nanosci Nanotechnol ; 13(8): 5474-80, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23882781

ABSTRACT

We report results of an attempt to create nanostructures on polyethylene terephthalate substrate using the interference lithography and plasma etching technique. Methods to create nanogrooves, nanopillars, nanofins and nanoholes have been presented. The effects of chemical and physical etching associated with plasma etching on the synthesis of nanostructures were examined in detail. Different etch rates and anisotropy as a function of plasma power and pressure were reported and explained, offering good understanding of the physics of the etching process. Ways to improve anisotropy have been suggested and experimentally verified. We show that this method can produce nanostructured substrate with wide surface coverage and good uniformity. The flexibility of this method was demonstrated in that the period and shapes of the nanopattern can be varied easily without resorting to complicated fabrication processes and machinery. Our method brings forth an easy and cost-effective way to create uniform nanostructures on a large area in a controllable fashion.

6.
Langmuir ; 28(31): 11465-71, 2012 Aug 07.
Article in English | MEDLINE | ID: mdl-22783970

ABSTRACT

The capillary rise of liquid on a surface, or "wicking", has potential applications in biological and industrial processes such as drug delivery, oil recovery, and integrated circuit chip cooling. This paper presents a theoretical study on the dynamics of wicking on silicon nanopillars based on a balance between the driving capillary forces and viscous dissipation forces. Our model predicts that the invasion of the liquid front follows a diffusion process and strongly depends on the structural geometry. The model is validated against experimental observations of wicking in silicon nanopillars with different heights synthesized by interference lithography and metal-assisted chemical etching techniques. Excellent agreement between theoretical and experimental results, from both our samples and data published in the literature, was achieved.


Subject(s)
Gold/chemistry , Nanostructures/chemistry , Silicon/chemistry , Capillary Action , Diffusion , Kinetics , Nanotechnology , Particle Size , Thermodynamics , Wettability
7.
Langmuir ; 27(7): 4126-33, 2011 Apr 05.
Article in English | MEDLINE | ID: mdl-21355585

ABSTRACT

We describe a new method of fabricating large-area, highly scalable, "hybrid" superhydrophobic surfaces on silicon (Si) substrates with tunable, spatially selective adhesion behavior by controlling the morphologies of Si nanowire arrays. Gold (Au) nanoparticles were deposited on Si by glancing-angle deposition, followed by metal-assisted chemical etching of Si to form Si nanowire arrays. These surfaces were chemically modified and rendered hydrophobic by fluorosilane deposition. Au nanoparticles with different size distributions resulted in the synthesis of Si nanowires with very different morphologies (i.e., clumped and straight nanowire surfaces). The difference in nanowire morphology is attributed to capillary force-induced nanocohesion, which is due to the difference in nanowire porosity. The clumped nanowire surface demonstrated the lotus effect, and the straighter nanowires demonstrated the ability to pin water droplets while maintaining large contact angles (i.e., the petal effect). The high contact angles in both cases are explained by invoking the Cassie-Baxter wetting state. The high adhesion behavior of the straight nanowire surface may be explained by a combination of attractive van der Waals forces and capillary adhesion. We demonstrate the spatial patterning of both low- and high-adhesion superhydrophobicity on the same substrate by the simultaneous synthesis of clumped and straight silicon nanowires. The demonstration of hybrid superhydrophobic surfaces with spatially selective, tunable adhesion behavior on single substrates paves the way for future applications in microfluidic channels, substrates for biologically and chemically based analysis and detection where it is necessary to analyze a particular droplet in a defined location on a surface, and as a platform to study in situ chemical mixing and interfacial reactions of liquid pearls.


Subject(s)
Nanostructures/chemistry , Nanotechnology/methods , Silicon/chemistry , Wettability , Nanowires/chemistry , Surface Properties
8.
Physiol Res ; 70(3): 401-412, 2021 07 12.
Article in English | MEDLINE | ID: mdl-33982581

ABSTRACT

High dependency of arterial blood pressure (ABP) on enhanced sympathetic activity, which maintains vascular tone, leads to hypotension after hemodynamic insults that blunt the sympathetic activity. Therefore, we hypothesized that sympathovagal balance before tourniquet deflation (TD) determines the extent of a reduction in ABP after TD during total knee arthroplasty (TKA). Fifty-four hypertensive female patients undergoing TKA under spinal anesthesia were analyzed. The sympathovagal balance [low-to-high frequency ratio of heart rate variability (LF/HF)] before TD was defined as (LF/HF during 5 min before TD-preanesthetic LF/HF)/preanesthetic LF/HF (%). An increase in its value represents a shift in sympathovagal balance toward sympathetic predominance. The percent change in the mean ABP (MAP) after TD was defined as (minimum MAP during 10 min after TD-averaged MAP during 5 min before TD)/averaged MAP during 5 min before TD (%). Simple linear regression was performed to assess the correlation between the sympathovagal balance before TD and change in MAP after TD. The correlation was also assessed by multiple linear regression controlling for age, duration of tourniquet inflation, and spinal anesthesia-induced hypotension. Thirty-two minutes (on average) after tourniquet inflation, the MAP was decreased by 12.1 (-3.0 to 47.9) % [mean (range)] upon TD (P<0.001). The sympathovagal balance before TD was negatively proportional to the change in MAP after TD in both simple and multiple linear regression models (R2=0.323 and 0.340, P<0.001). A shift in sympathovagal balance toward sympathetic predominance before TD is associated with a decrease in ABP after TD.


Subject(s)
Arterial Pressure , Arthroplasty, Replacement, Knee , Sympathetic Nervous System/physiopathology , Tourniquets , Aged , Aged, 80 and over , Aging , Anesthesia, Spinal , Female , Heart Rate , Humans , Hypertension/physiopathology , Intraoperative Period , Middle Aged , Treatment Outcome , Vagus Nerve/physiopathology
9.
Nanotechnology ; 21(20): 205305, 2010 May 21.
Article in English | MEDLINE | ID: mdl-20418606

ABSTRACT

We report a simple and cost effective method for the synthesis of large-area, precisely located silicon nanocones from nanowires. The nanowires were obtained from our interference lithography and catalytic etching (IL-CE) method. We found that porous silicon was formed near the Au catalyst during the fabrication of the nanowires. The porous silicon exhibited enhanced oxidation ability when exposed to atmospheric conditions or in wet oxidation ambient. Very well located nanocones with uniform sharpness resulted when these oxidized nanowires were etched in 10% HF. Nanocones of different heights were obtained by varying the doping concentration of the silicon wafers. We believe this is a novel method of producing large-area, low cost, well defined nanocones from nanowires both in terms of the control of location and shape of the nanocones. A wide range of potential applications of the nanocone array can be found as a master copy for nanoimprinted polymer substrates for possible biomedical research; as a candidate for making sharp probes for scanning probe nanolithography; or as a building block for field emitting tips or photodetectors in electronic/optoelectronic applications.


Subject(s)
Metal Nanoparticles/chemistry , Nanotechnology/methods , Nanowires/chemistry , Silicon/chemistry , Catalysis , Electronics , Equipment Design , Microscopy, Scanning Probe/instrumentation , Optics and Photonics
10.
J Nanosci Nanotechnol ; 9(2): 1577-81, 2009 Feb.
Article in English | MEDLINE | ID: mdl-19441574

ABSTRACT

Growth of germanium (Ge) nanocrystals in silicon (Si) oxide and hafnium aluminum oxide (HfAlO) is examined. In Si oxide, nanocrystals were able to form at annealing temperatures of 800 degrees C to 1000 degrees C. Nanocrystals formed at 800 degrees C were round and approximately 8 nm in diameter, at 900 degrees C they become facetted and at 1000 degrees C they become spherical again. In HfAlO, at 800 degrees C nanocrystals formed are relatively smaller (approximately 3 nm in diameter) and lower in density. While at 900 degrees C and 1000 degrees C, nanocrystals did not form due to out-diffusion of Ge. Different nanocrystal formation characteristics in the matrices are attributed to differences in their crystallization temperatures.

11.
J Phys Condens Matter ; 21(18): 185005, 2009 May 06.
Article in English | MEDLINE | ID: mdl-21825451

ABSTRACT

A study of the electronic structure and magnetic properties of Co doped ZnO thin films synthesized by ion implantation followed by swift heavy ion irradiation is presented using near-edge x-ray absorption fine structure (NEXAFS) and x-ray magnetic circular dichroism (XMCD) measurements. The spectral features of NEXAFS at the Co L(3,2)-edge show entirely different features than that of metallic Co clusters and other Co oxide phases. The atomic multiplet calculations are performed to determine the valence state, symmetry and the crystal field splitting, which show that in the present system Co is in the 2+ state and substituted at the Zn site in tetrahedral symmetry with 10Dq = -0.6 eV. The ferromagnetic character of these materials is confirmed through XMCD spectra. To rule out the possibilities of defect induced magnetism, the results are compared with Ar annealed and Ar-ion implanted pure ZnO thin films. The presented results confirm the substitution of Co at the Zn site in the ZnO matrix, which is responsible for room temperature ferromagnetism.

12.
J Nanosci Nanotechnol ; 8(10): 5566-70, 2008 Oct.
Article in English | MEDLINE | ID: mdl-19198500

ABSTRACT

Locally distributed crystalline ZnSiO3 nanoparticles embedded in a SiO2 layer inserted between the ZnO thin film and the Si substrate were formed using transmission electron microscopy (TEM) with a focused electron beam irradiation process. High-resolution TEM (HRTEM) images and energy dispersive X-ray spectroscopy (EDS) profiles showed that ZnSiO3 nanocrystals with a size of approximately 6 nm were formed in the SiO2 layer. The formation mechanisms of the ZnSiO3 nanocrystals in the SiO2 layer are described on the basis of the HRTEM images and the EDS profiles.

13.
Transplant Proc ; 50(10): 3621-3625, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30577247

ABSTRACT

BACKGROUND: The balance between T helper 1 (Th1) and T helper 2 (Th2) signature cytokines plays a critical role in the immune response. The aim of this study was to evaluate the Th1 to Th2 cytokine ratio in healthy persons and patients with cirrhotic hepatitis and to investigate changes in the Th1 to Th2 cytokine ratio during living donor liver transplantation (LDLT) surgery. METHODS: Eighty patients were allocated to each of the donor and recipient groups. In the recipient group, signature cytokines-interferon gamma (IFN-γ) and tumor necrosis factor α (TNF-α) as Th1 and interleukin 6 (IL-6) and interleukin 10 (IL-10) as Th2-were quantified after induction of anesthesia (baseline, stage 1), 60 minutes after the start of the anhepatic phase (stage 2), and 60 minutes after reperfusion (stage 3). In the donor group, cytokine levels were analyzed only at stage 1. The Th1/Th2 cytokine ratios at baseline and over time during surgery in the recipient group were evaluated. RESULTS: At stage 1, the recipient group exhibited higher levels of all cytokines than the donor group. However, the IFN-γ/IL-6, IFN-γ/IL-10, TNF-α/IL-6, and TNF-α/IL-10 ratios of the groups were comparable. The levels of all cytokines, except IFN-γ, increased during LDLT. The IFN-γ/IL-6, IFN-γ/IL-10, TNF-α/IL-6, and TNF-α/IL-10 ratios declined significantly during LDLT. CONCLUSIONS: The preoperative Th1/Th2 cytokine ratios were similar in healthy persons and patients with cirrhotic hepatitis. During LDLT surgery, Th2 activity was enhanced, as indicated by a shift in the Th1/Th2 cytokine ratio toward Th2.


Subject(s)
Cytokines/immunology , Liver Transplantation , Living Donors , Th1 Cells/immunology , Th2 Cells/immunology , Adult , Cytokines/blood , Female , Humans , Interferon-gamma/blood , Interferon-gamma/immunology , Interleukin-10/blood , Interleukin-10/immunology , Interleukin-6/blood , Interleukin-6/immunology , Male , Middle Aged , Prospective Studies , Tumor Necrosis Factor-alpha/blood , Tumor Necrosis Factor-alpha/immunology
14.
Sci Rep ; 8(1): 4851, 2018 Mar 19.
Article in English | MEDLINE | ID: mdl-29555981

ABSTRACT

We propose the unique structure of highly dispersible single-walled carbon nanotubes (SWCNTs) in various solvents and polymers using the ZnO nano particle template. Buckled nanospring-shaped carbon nanotubes (NS-CNTs) were synthesized by a chemical reaction of ZnO nanoparticles with acid-treated SWCNTs and then dissolving ZnO through chemical etching. The unique structure of distorted hexagonal NS-CNTs encircled around ZnO nanoparticles was formed by the bending of SWCNTs caused by the agglomeration of chemically adsorbed Zn(OH)2, which is further crystallized as the polycrystalline ZnO inner core. The highly dispersible NS-CNTs could be incorporated in the poly[(vinylidenefluoride-co-trifluoroethylene] [P(VDF-TrFE)] copolymer, one of widely studied ferro- and piezo-electric polymer, up to the value of 15 wt% as nanofillers. The relative dielectric constant (K) of polymer nanocomposite, at 1 kHz, was greatly enhanced from 12.7 to the value of 62.5 at 11 wt% of NS-CNTs, corresponding to a 492% increase compared to that of pristine P(VDF-TrFE) with only a small dielectric loss tangent (D) of 0.1.

15.
Int J Law Psychiatry ; 47: 68-73, 2016.
Article in English | MEDLINE | ID: mdl-27021135

ABSTRACT

Prompted by four questions, forensic mental health clinicians from Russia, China, Japan, Hong Kong, Australia and New Zealand provided information on both the legislative basis and current practice concerning the relationship between legal insanity, intoxication and drug induced psychosis in their six Pacific Rim Countries which account for nearly 20% of the world's population. Details of the survey for each contributing nation are provided. While there are significant variations in practice that have been shaped by regional legal, clinical and cultural influences there is considerable similarity in the legislation underpinning how these issues are considered. Consequently there remain similar challenges for each nation. In none of the legislative bases was the issue of drug induced psychosis specifically addressed. The authors conclude that evolving pharmaco-neuropsychiatric knowledge, societal values and patterns of substance misuse require nations to consider developments in scientific and clinical knowledge to support their interpretations of the relationship between altered mental states as a result of substance use and the legal construct of insanity.


Subject(s)
Cross-Cultural Comparison , Illicit Drugs/legislation & jurisprudence , Illicit Drugs/toxicity , Insanity Defense , Liability, Legal , Psychoses, Substance-Induced/diagnosis , Psychoses, Substance-Induced/psychology , Substance-Related Disorders/diagnosis , Substance-Related Disorders/psychology , Amphetamine-Related Disorders/diagnosis , Amphetamine-Related Disorders/psychology , Australia , China , Hong Kong , Humans , Japan , Methamphetamine/toxicity , New Zealand , Russia
16.
Nanoscale ; 7(25): 11123-34, 2015 Jul 07.
Article in English | MEDLINE | ID: mdl-26059556

ABSTRACT

Metal assisted anodic etching (MAAE) of Si in HF, without H2O2, is demonstrated. Si wafers were coated with Au films, and the Au films were patterned with an array of holes. A Pt mesh was used as the cathode while the anodic contact was made through either the patterned Au film or the back side of the Si wafer. Experiments were carried out on P-type, N-type, P(+)-type and N(+)-type Si wafers and a wide range of nanostructure morphologies were observed, including solid Si nanowires, porous Si nanowires, a porous Si layer without Si nanowires, and porous Si nanowires on a thick porous Si layer. Formation of wires was the result of selective etching at the Au-Si interface. It was found that when the anodic contact was made through P-type or P(+)-type Si, regular anodic etching due to electronic hole injection leads to formation of porous silicon simultaneously with metal assisted anodic etching. When the anodic contact was made through N-type or N(+)-type Si, generation of electronic holes through processes such as impact ionization and tunnelling-assisted surface generation were required for etching. In addition, it was found that metal assisted anodic etching of Si with the anodic contact made through the patterned Au film essentially reproduces the phenomenology of metal assisted chemical etching (MACE), in which holes are generated through metal assisted reduction of H2O2 rather than current flow. These results clarify the linked roles of electrical and chemical processes that occur during electrochemical etching of Si.

17.
J Nanosci Nanotechnol ; 15(6): 4332-8, 2015 Jun.
Article in English | MEDLINE | ID: mdl-26369045

ABSTRACT

Cobalt/Palladium (Co/Pd) multilayer film and nanodisc samples were fabricated on polyethylene terephthalate (PET) substrates. The effects of surface roughness and grain size of PET substrate, the Co/Pd layer and the Au intermediate layer on the magnetic properties of these samples were investigated. We observed that the coercivity for Co/Pd films deposited directly on a smoother PET substrate is significantly smaller when compared with Co/Pd films deposited at the same time on Au buffer layer. The patterned Co/Pd nanodisc array exhibited a larger coercivity than the corresponding continuous film due to lower probability of finding nucleation sites in reduced film area.

18.
J Nanosci Nanotechnol ; 15(7): 4926-33, 2015 Jul.
Article in English | MEDLINE | ID: mdl-26373058

ABSTRACT

Thin film microbatteries require electrode materials with high areal specific capacities and good cyclability. Use of vapor-deposited silicon thin films as anodes in Li-ion microbatteries offers the advantage of high capacity as well as compatibility with other processes used for microsystem fabrication. Unfortunately, monolithic silicon films greater than 200 nm in thickness pulverize during lithiation and delithiation. We have used metal-assisted-chemical-etching of sputter-deposited amorphous silicon films to make nanoporous silicon layers and arrays of silicon nanopillars as a means of achieving anodes with high areal capacity and good cyclability. We have compared the performance of these nanostructured layers with the performance of monolithic silicon films in Li half-cells. A reduced first cycle coulombic efficiency was observed in all cases and was attributed to the irreversible formation of Li2O due to the presence of oxygen in the sputter-deposited silicon films. This was controlled through modifications of the sputtering conditions. As expected, monolithic films thicker than 200 nm showed poor cycling performance due to pulverization of the film. Nanoporous silicon showed good initial cycling performance but the performance degraded due to porosity collapse and delamination. Arrays of silicon nanopillars made from 750 nm silicon films exhibited good cycling, rate performance and an areal capacity (0.20 mA h cm(-2)) 1.6 times higher than what could be obtained with monolithic Si films with similar cyclability.

19.
Pediatrics ; 104(4 Pt 2): 1018-21, 1999 Oct.
Article in English | MEDLINE | ID: mdl-10506255

ABSTRACT

The insulin-like growth factor (IGF) binding proteins (IGFBPs) were initially identified as carrier proteins for IGF-I and IGF-II in a variety of biologic fluids. Their presumed function was to protect IGF peptides from degradation and clearance, increase the half-life of the IGFs, and deliver them to appropriate tissue receptors. The concept of IGFBPs as simple carrier proteins has been complicated, however, by a number of observations: 1) the six IGFBPs vary in their tissue expression and their regulation by other hormones and growth factors; 2) the IGFBPs are subjected to proteolytic degradation, thereby altering their affinities for the IGFs; 3) IGFBP-3 and IGFBP-5, in addition to binding IGFs, also can associate with an acid-labile subunit, thereby increasing further the half-life of the IGFs; 4) in addition to modifying the access of IGF peptides to IGF and insulin receptors, several of the IGFBPs may be capable of increasing IGF action; 5) some of the IGFBPs may be capable of IGF-independent regulation of cell growth; 6) some of the IGFBPs are associated with cell membranes or possibly with membrane receptors; and 7) some of the IGFBPs have nuclear recognition sites and may be found within the nucleus. Additionally, a number of cDNAs identified recently have been found to encode proteins that bind IGFs, but with substantially lower affinities than is the case with IGFBPs. The N-terminal regions of the predicted proteins are structurally homologous to the classic IGFBPs, with conservation of the cysteine-rich region. These observations suggest that these low-affinity binders are members of an IGFBP superfamily, capable of regulating cell growth by both IGF-dependent and IGF-independent mechanisms.insulin-like growth factor, insulin-like growth factor binding proteins.


Subject(s)
Insulin-Like Growth Factor Binding Proteins , Humans , Insulin-Like Growth Factor Binding Proteins/classification , Insulin-Like Growth Factor Binding Proteins/physiology , Molecular Weight
20.
J Endocrinol ; 169(1): 97-110, 2001 Apr.
Article in English | MEDLINE | ID: mdl-11250651

ABSTRACT

Dietary factors play an important role in both the development and prevention of human cancers, including breast carcinoma. One dietary micronutrient, sodium butyrate (NaB), is a major end product of dietary starch and fiber, produced naturally during digestion by anaerobic bacteria in the cecum and colon. NaB is a potent growth inhibitor and initiates cell differentiation for many cell types in vitro. In this study, we investigated the effects of NaB on three human mammary epithelial cells and regulation of the IGF axis, specifically, IGF-binding protein-3 (IGFBP-3), a known growth regulator in human mammary cells, and IGFBP-related protein 2 (IGFBP-rP2)/connective tissue growth factor. NaB inhibited DNA synthesis, as measured by [3H]thymidine incorporation, in estrogen-responsive (MCF-7) and estrogen-non-responsive (Hs578T) breast cancer cells, and normal human mammary epithelial cells (HMEC) to a similar degree (up to 90% inhibition at 1-10 mM concentrations). Treatment of cells with NaB induced histone hyperacetylation, suggesting that NaB exerts its biological effects, at least in part, as a histone deacetylase inhibitor in mammary epithelial cells. Treatment of Hs578T cells with NaB caused an induction of apoptotic cell death. NaB treatment resulted in increased levels of p21(Waf1/Cip1) mRNA and protein in Hs578T cells and distinct upregulation of p27(Kip1) in HMEC, suggesting that NaB activates different genes involved in cell cycle arrest, depending upon the cell type. In the same context, among the IGFBP superfamily members tested, NaB specifically upregulated the expression of IGFBP-3 and IGFBP-rP2. These two proteins are known to be involved in inhibition of mammary epithelial cell replication. Northern blot analysis showed that NaB treatment at 1-10 mM concentrations caused a dose-dependent stimulation of IGFBP-3 mRNA expression in cancerous cells and IGFBP-rP2 mRNA expression in both cancerous and non-cancerous cells. Protein data from Western ligand blot and immunoblot analyses demonstrated parallel results. In summary, we have demonstrated that NaB (i) uniformly suppresses DNA synthesis in both cancerous and non-cancerous mammary cells, and (ii) upregulates IGFBP-3 and IGFBP-rP2 mRNA and protein levels in cancerous and non-cancerous mammary cells. These results provide the first demonstration that butyrate regulates the IGFBP system in the human mammary system.


Subject(s)
Breast Neoplasms/metabolism , Breast/metabolism , Butyrates/pharmacology , Cell Cycle Proteins , Insulin-Like Growth Factor Binding Proteins/metabolism , Intercellular Signaling Peptides and Proteins , Micronutrients/pharmacology , Tumor Suppressor Proteins , Acetylation , Apoptosis , Blotting, Northern , Blotting, Western , Breast/drug effects , Cells, Cultured , Connective Tissue Growth Factor , Cyclin-Dependent Kinase Inhibitor p21 , Cyclin-Dependent Kinase Inhibitor p27 , Cyclins/metabolism , Enzyme Inhibitors/metabolism , Epithelium/drug effects , Epithelium/metabolism , Female , Growth Substances/metabolism , Histones/metabolism , Humans , Immediate-Early Proteins/metabolism , Insulin-Like Growth Factor Binding Protein 3/metabolism , Microtubule-Associated Proteins/metabolism , Tumor Cells, Cultured
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