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1.
Bioinorg Chem Appl ; 2022: 8440756, 2022.
Article in English | MEDLINE | ID: mdl-35308018

ABSTRACT

Green synthesis of metal oxide nanoparticles (NPs) is a viable alternative methodology because of cost-effective and availability of environmentally friendly templates for desired application, which has attracted the attention of researchers in recent years. In the present study, Co3O4 NPs were synthesized in various volume ratios in the presence of Solanum tuberosum leaf extract as a template. The synthesized Co3O4 NPs were characterized by X-ray diffraction (XRD), scanning electron microscopy-energy dispersive X-ray spectroscopy (SEM-EDX), transmission electron microscopy (TEM), high resolution transmission electron microscopy (HRTEM), surface area electron diffraction (SAED), UV-Vis diffuse reflectance spectroscopy (UV-DRS), and Fourier transform infrared (FTIR) spectroscopy. XRD analysis found that the average crystalline sizes for the 1 : 2, 1 : 1, and 2 : 1 volume ratios was 25.83, 21.05, and 27.98 nm, respectively. SEM-EDX and TEM analyses suggest that the green-synthesized Co3O4 NPs are spherical in shape without the presence of impurities. The band gap E g values of the 1 : 2, 1 : 1, and 2 : 1 volume ratios of Co3O4 NPs were found to be 1.83, 1.77, and 2.19 eV, respectively. FTIR analysis confirmed the presence of various bioactive ingredients within the leaf extract of Solanum tuberosum. Co3O4 NPs-modified electrodes showed better sensing capability towards ascorbic acid and citric acid due to enhanced electron transfer kinetics. Among three volume ratios (1 : 2, 1 : 1, and 2 : 1) of Co3O4 nanoelectrodes, 1 : 1 and 2 : 1 were identified as the best performing nanoelectrodes. This is possibly due to the high catalytic behavior and the more homogenized surface structure. Co3O4 (1 : 2) nanodrug showed the enhanced antibacterial activity (16 mm) towards S. aureus which is attributed to the formation of enhanced reactive oxygen species (ROS).

2.
Int J Surg Case Rep ; 16: 37-8, 2015.
Article in English | MEDLINE | ID: mdl-26410805

ABSTRACT

INTRODUCTION: Hematogenous spread of bacteria from the bowel due to bacterial translocation has been postulated in animal and trauma studies. This case presents a patient with possible hematogenous bacterial spreading after acute laparotomy. CASE PRESENTATION: A 57-year old woman was admitted with abdominal pain. A computed tomography showed mechanical small bowel obstruction. A laparotomy was performed showing no contamination, and no bowel resection was performed. The patient was not given any antibiotics during this time. The patient was re-admitted 24h after discharge with fever, elevated white count and abdominal pain. A computed tomography showed newly developed intrahepatic abscesses. These were treated with antibiotics, and the patient was discharged with follow-up ultrasound showing diminished abscesses. DISCUSSION: This case discusses the possible pathophysiology behind the development of intrahepatic abscesses after small bowel obstruction. CONCLUSION: Febrilia and pain in upper right quadrant of the abdomen days after a simple operation for bowel obstruction could be caused by translocation of intestinal bacteria and subsequent formation of hepatic abscesses.

3.
Article in English | MEDLINE | ID: mdl-25314464

ABSTRACT

A bimesogen, BR1, composed of a bent-core and calamitic unit, linked laterally via a flexible spacer is investigated by dielectric and electro-optic techniques. X-ray results show the presence of clusters in the nematic phase, and the cluster size is of the order of the thickness of a single layer. The splitting of the small-angle scattering Δχ/2 is about 50°, which indicates SmC like clusters with a significant tilt of the molecules in the quasilayers. The sign reversal of the dielectric anisotropy Δε' is observed as a function of frequency; the behavior is rather similar to that exhibited by the conventional dual frequency nematics, composed of a calamitic mesogen, with the exception that it occurs at much lower frequencies in this material. Interestingly, as the bimesogen enters its nematic phase, the average permittivity decreases as the temperature is lowered. This indicates the onset of antiparallel association of some of the dipoles in the system, and this type of association is much more prominent in BR1 in comparison to other bent-core liquid crystalline systems composed of the same bisbenzoate core unit. The analysis of the dielectric spectra using the Maier-Meier model confirms the onset of an antiparallel correlation of dipoles occurring at the isotropic to nematic phase transition temperature. Additionally these results support a model of the cluster where the transverse dipole moments in the neighboring layers are antiparalleled to each other.


Subject(s)
Liquid Crystals , Optical Phenomena , Electric Impedance , Temperature
4.
Article in English | MEDLINE | ID: mdl-24125281

ABSTRACT

We report results of the splay (K_{11}) and bend (K_{33}) elastic constants and the effective flexoelectric coefficient of three bent-core liquid crystals belonging to a homologous series of 4-cyanoresorcinol bisbenzoates with varying chain lengths. Based on the results of x-ray scattering studies, one of the three compounds with a shorter chain length (C4) has few, if any, clusters present in its nematic phase and behaves quite normally, whereas the others two with longer chain lengths (C6 and C7) show the presence of cybotactic nematic phase with smectic C type clusters. These grow in size with a reduction in temperature. K_{33} is found to be the least for C7, whereas it is weakly dependent on temperature. K_{33} is somewhat higher for C4 and C6 and is almost independent of temperature. K_{11} for C6 and C7 is higher by 20% to 50% than C4 depending on the temperature. K_{11} increases linearly with a reduction in temperature for the three compounds. For C6 K_{11}>K_{33} by a factor up to ∼2 depending on the temperature, for C4 it is greater by a factor up to 1.3, and for C7 it is greater by a factor of ∼2.5. These results suggest that the clusters do not have any effect on K_{11}. The magnitude of the effective flexoelectric coefficient e=(|e_{1}-e_{3}|) is measured by creating a uniform lying helix (ULH) configuration in a planar cell. By doping the bent-core system with a small wt% of a chiral dopant, the ULH is obtained by cooling planar cells to the cholesteric phase under weak electric field. The effective flexoelectric coefficient is greater for the bent-core systems than for calamatics but it is much lower than would otherwise have been expected for such systems. |e_{1}-e_{3}| for C4 > C6 ≈ C7 is greater by 20% to 25% than C6 and C7 at the same reduced temperature. These differences in the effective flexoelectric coefficient can easily arise from a difference in the chain lengths among the members of the series but if the presence of clusters were to have an influence on |e_{1}-e_{3}|, then these would reduce it, contrary to the expectations for the bent-core systems.

5.
J Laryngol Otol ; 126(4): 345-8, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22310164

ABSTRACT

BACKGROUND: The Bluetooth wireless headset has been promoted as a 'hands-free' device with a low emission of electromagnetic radiation. OBJECTIVE: To evaluate potential changes in hearing function as a consequence of using Bluetooth devices, by assessing changes in pure tone audiography and distortion production otoacoustic emissions. DESIGN: Prospective study. MATERIALS AND METHODS: Thirty adult volunteers were exposed to a Bluetooth headset device (1) on 'standby' setting for 6 hours and (2) at full power for 10 minutes. Post-exposure hearing was evaluated using pure tone audiography and distortion production otoacoustic emission testing. RESULTS: There were no statistically significant changes in hearing, as measured above, following either exposure type. CONCLUSION: Exposure to the electromagnetic field emitted by a Bluetooth headset, as described above, did not decrease hearing thresholds or alter distortion product otoacoustic emissions.


Subject(s)
Cell Phone , Electromagnetic Fields/adverse effects , Hearing/radiation effects , Wireless Technology , Adult , Audiometry, Pure-Tone , Auditory Threshold/radiation effects , Cochlea , Female , Hearing Loss , Humans , Male , Otoacoustic Emissions, Spontaneous/physiology , Pilot Projects , Prospective Studies , Young Adult
6.
Med J Malaysia ; 66(2): 152-3, 2011 Jun.
Article in English | MEDLINE | ID: mdl-22106701

ABSTRACT

The use of an endoscopic approach for the division of glottic webs or stenosis has been reported in the literature and has been mainly confined to the anterior commisure. We report a rare case of caustic injury to the upper aerodigestive tract that resulted in extensive web formation along the membranous vocal cord which was successfully treated with endoscopic lysis of the adhesions and the use of a silastic sheet keel as a stent.


Subject(s)
Burns, Inhalation/complications , Caustics/adverse effects , Endoscopy , Glottis , Laryngostenosis/etiology , Laryngostenosis/therapy , Adult , Burns, Inhalation/pathology , Burns, Inhalation/therapy , Female , Humans , Laryngostenosis/pathology
7.
Proc Inst Mech Eng H ; 224(5): 633-49, 2010.
Article in English | MEDLINE | ID: mdl-20718268

ABSTRACT

Image-guided robots have been widely used for bone shaping and percutaneous access to interventional sites. However, due to high-accuracy requirements and proximity to sensitive nerves and brain tissues, the adoption of robots in inner-ear surgery has been slower. In this paper the authors present their recent work towards developing two image-guided industrial robot systems for accessing challenging inner-ear targets. Features of the systems include optical tracking of the robot base and tool relative to the patient and Kalman filter-based data fusion of redundant sensory information (from encoders and optical tracking systems) for enhanced patient safety. The approach enables control of differential robot positions rather than absolute positions, permitting simplified calibration procedures and reducing the reliance of the system on robot calibration in order to ensure overall accuracy. Lastly, the authors present the results of two phantom validation experiments simulating the use of image-guided robots in inner-ear surgeries such as cochlear implantation and petrous apex access.


Subject(s)
Ear, Inner/surgery , Image Processing, Computer-Assisted , Otologic Surgical Procedures/methods , Robotics/methods , Surgery, Computer-Assisted/methods , Algorithms , Equipment Design , Humans , Motion , Otologic Surgical Procedures/instrumentation , Phantoms, Imaging , Robotics/instrumentation , Surgery, Computer-Assisted/instrumentation
9.
J Pharmacol Exp Ther ; 296(2): 364-71, 2001 Feb.
Article in English | MEDLINE | ID: mdl-11160619

ABSTRACT

The pentacyclic palmarumycins are structurally unique natural products with both antifungal and antibacterial activities but their antineoplastic effects are not well established. We have examined their antiproliferative actions against tumor cells using a temperature-sensitive tsFT210 mouse mammary carcinoma cell line and found that a novel palmarumycin analog, [8-(furan-3-ylmethoxy)-1-oxo-1,4-dihydronaphthalene-4-spiro-2'-naphtho[1",8"-de][1',3'][dioxin] or SR-7, prominently blocked mammalian cell cycle transition in G2/M but not in G1 phase. We found no evidence for inhibition of the critical mitosis-controlling cyclin-dependent kinase Cdk1, or its regulator, the dual specificity phosphatase Cdc25. Moreover, Cdk1 was hypophosphorylated and not directly inhibited by SR-7. SR-7 also failed in vitro to hypernucleate bovine tubulin, did not compete with colchicine for tubulin binding, and only modestly blocked GTP-induced assembly. In addition, SR-7 caused almost equal inhibition of paclitaxel-sensitive and -resistant cell growth. Moreover, unlike benchmark tubulin-disrupting agents, SR-7 did not cause hyperphosphorylation of the antiapoptotic protein Bcl-2. Thus, SR-7 represents a novel chemical structure that can inhibit G2/M transition by a mechanism that appears to be independent of marked tubulin disruption.


Subject(s)
Antineoplastic Agents/pharmacology , Breast Neoplasms/pathology , Dioxanes/pharmacology , Spiro Compounds/pharmacology , Animals , Binding, Competitive/drug effects , Blotting, Western , Breast Neoplasms/metabolism , Cell Division/drug effects , Colchicine/metabolism , Cyclin-Dependent Kinases/metabolism , Female , Fibroblasts/drug effects , Flow Cytometry , Humans , Mice , Naphthalenes , Phosphoric Monoester Hydrolases/metabolism , Phosphorylation , Proto-Oncogene Proteins c-bcl-2/metabolism , Receptors, Estrogen/drug effects , Tubulin/metabolism , Tumor Cells, Cultured , Tumor Suppressor Protein p53/metabolism
10.
Prostate ; 45(4): 277-88, 2000 Dec 01.
Article in English | MEDLINE | ID: mdl-11102952

ABSTRACT

BACKGROUND: Z-1,1-Dichloro-2,3-diphenylcyclopropane (A(II)) has long been known to be active against models of breast carcinoma. Microtubule perturbation and interaction at type II estrogen binding sites mediate its actions. METHODS: Since these targets are potentially useful for treatment of prostate tumors, we studied the drug's effects on androgen-sensitive (LNCaP) and -independent (PC-3) human prostatic carcinoma lines. Effects on cell growth and morphology, prostate-specific antigen (PSA) expression, and cell cycle kinetics were determined by microscopy, antibody-based methods, flow cytometry, and electrophoresis. RESULTS: At 100 microM, A(II) reduced survival of both lines by 50% in 12-24 hr, whereas 10 microM A(II) caused a prolonged block of proliferation in both lines, and parallel and complete block of PSA in LNCaP cells. At 10 microM, A(II) caused no major changes in chromatin, morphology or cell cycle distributions, whereas 100 microM drug caused rapid, large-scale cell detachment, nuclear and internucleosomal DNA fragmentation, and hypodiploidy. These effects were also accompanied by dissolution of cellular microtubule arrays. A more potent tubulin assembly-inhibiting congener of A(II), Z-1, 1-dichloro-2-(4-methoxy-phenyl)-3-phenylcyclopropane, slightly more effectively inhibited cell growth, caused little hypodiploidy, but potently and dose-dependently caused G(2)/M accumulation. CONCLUSIONS: These and previous data suggest that the Z-1, 1-dichloro-2,3-diarylcyclo-propanes may be useful in the treatment of human prostate disease.


Subject(s)
Antineoplastic Agents/pharmacology , Apoptosis/drug effects , Prostate-Specific Antigen/antagonists & inhibitors , Tamoxifen/analogs & derivatives , Tamoxifen/pharmacology , Androgens/physiology , Cell Cycle/drug effects , Cell Division/drug effects , DNA Fragmentation , Dose-Response Relationship, Drug , Estrogen Receptor Modulators/pharmacology , Growth Inhibitors/pharmacology , Humans , Male , Neoplasms, Hormone-Dependent/drug therapy , Neoplasms, Hormone-Dependent/immunology , Neoplasms, Hormone-Dependent/pathology , Prostate-Specific Antigen/biosynthesis , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/immunology , Prostatic Neoplasms/pathology , Tumor Cells, Cultured/drug effects
11.
Biochem Pharmacol ; 57(1): 97-110, 1999 Jan 01.
Article in English | MEDLINE | ID: mdl-9920290

ABSTRACT

We have shown previously that Z-1,1-dichloro-2,3-diphenylcyclopropane (a.k.a. Analog II, A(II)) inhibits human breast cancer cell proliferation regardless of estrogen receptor status or estrogen sensitivity, and that its cellular targets include microtubules. In the present study, we investigated the apoptosis-inducing effects of A(II). MCF-7, MCF-7/LY2, and MDA-MB-231 cells all showed nuclear fragmentation in response to 100 microM A(II) when stained with Hoechst 33342 and examined by fluorescence microscopy. Pulsed field gel electrophoretic analysis showed that each of the cell lines also developed specific high molecular weight DNA fragments: a low level of 1-2 Mb fragments appeared after 6 hr, while 30-50 kb fragments accumulated subsequently. At 24 hr of drug exposure, the majority of cells became nonadherent, and the 30-50 kb fragments were restricted to detached MCF-7 and MDA-MB-231 cells. Both adherent and detached MCF-7/LY2 cells exhibited these fragments. A previous study by single-color (propidium) flow cytometry demonstrated that A(II) blocks MDA-MB-231 cells in G2/M of the cell cycle. More refined analyses in the present study showed this same result for MDA-MB-231 cells, but MCF-7 and MCF-7/LY2 cells did not reveal apparent drug-induced cell cycle block. A(II) demonstrated growth inhibitory, cell cycle-perturbing, and hypodiploidy-inducing activity against other human breast carcinoma lines, i.e. BT-20, CAMA-1, and SKBR-3, but no such actions in the non-tumorigenic, "normal" human breast epithelial line MCF-10A. Bromodeoxyuridine labeling and two-color flow cytometric analysis, however, suggested that A(II) caused stimulation into S phase, and that G2/M was the phase of the cell cycle from which cells apoptosed. A(II) caused cell rounding, detachment from the growth matrix, and nuclear shrinkage and fragmentation in parallel with biochemical changes. Cycloheximide inhibited A(II)-induced cell death, indicating that its toxicity requires de novo protein synthesis.


Subject(s)
Antineoplastic Agents/toxicity , Apoptosis/drug effects , Cell Cycle/drug effects , Tamoxifen/analogs & derivatives , Benzimidazoles , Breast Neoplasms , Cell Cycle/physiology , Cell Nucleus/drug effects , Cell Nucleus/pathology , DNA Fragmentation , DNA, Neoplasm/drug effects , Electrophoresis, Gel, Pulsed-Field , Female , G2 Phase , Humans , Mitosis , Molecular Structure , Tamoxifen/toxicity , Tumor Cells, Cultured
12.
Ophthalmic Surg Lasers ; 30(7): 560-4, 1999.
Article in English | MEDLINE | ID: mdl-10929980

ABSTRACT

BACKGROUND AND OBJECTIVE: To determine the optimal wavelength for subconjunctival laser suture lysis. MATERIALS AND METHODS: 130 black monofilament 10-0 nylon sutures were sewn subconjunctivally into the bare sclera of enucleated rabbit globes. The lowest energy levels facilitating laser suture lysis were determined for the argon green (514.5 NM), argon blue-green (488.0 NM, 514.5 NM), and krypton red (647.1 NM) wavelengths. In addition, absorption spectroscopy was performed on the suture material and conjunctiva using the Perkin Elmer W/VIS Lambda 2 spectrometer. RESULTS: Krypton red produced the fewest buttonhole defects, and it was also the most efficient energy source for suture lysis (P = 0.0001) under nontenectomized conjunctiva. Absorbance spectra studies revealed peak absorbance at 628 NM for the 10-0 nylon suture material. CONCLUSIONS: Based on animal and absorption spectroscopy studies, krypton red may be a safer and more efficient wavelength for subconjunctival laser suture lysis.


Subject(s)
Conjunctiva/surgery , Laser Therapy/methods , Nylons , Ophthalmologic Surgical Procedures , Sclera/surgery , Sutures , Animals , In Vitro Techniques , Rabbits , Reproducibility of Results
13.
Brain Res Mol Brain Res ; 60(2): 270-81, 1998 Oct 01.
Article in English | MEDLINE | ID: mdl-9757062

ABSTRACT

Incubation of mock-transfected PC12 rat pheochromocytoma cells (PC12) for 2 h with increasing concentrations of glutamate caused progressive loss of viability (e.g., 67% with 15 mM glutamate). In contrast, the viability of bcl-2-transfected cells (PC12/bcl-2) was unaffected by glutamate. Neither PC12 nor PC12/bcl-2 cells showed a significant incidence of apoptosis in response to glutamate. Conventional phospholipid analysis by high-performance TLC and phosphorous determination showed no significant changes in the phospholipid composition of either cell line incubated with 5 mM glutamate. The peroxyl radical initiator 2,2'-azobis(2,4-dimethylvaleronitrile) caused a pronounced loss of all major phospholipid classes in PC12 cells, but no loss of cell viability. No phospholipid peroxidation was detected in PC12/bcl-2 cells incubated with

Subject(s)
Cell Survival/physiology , Genes, bcl-2 , Glutamic Acid/toxicity , Glutathione/metabolism , Phospholipids/metabolism , Proto-Oncogene Proteins c-bcl-2/metabolism , Adrenal Gland Neoplasms , Animals , Azo Compounds/pharmacology , Cell Survival/drug effects , Kinetics , Neoplasm Proteins/metabolism , Nitriles/pharmacology , Oxidation-Reduction , PC12 Cells , Pheochromocytoma , Proto-Oncogene Proteins c-bcl-2/genetics , Rats , Recombinant Proteins/biosynthesis , Recombinant Proteins/metabolism , Sulfhydryl Compounds/metabolism , Transfection
14.
Anticancer Drugs ; 9(1): 67-76, 1998 Jan.
Article in English | MEDLINE | ID: mdl-9491794

ABSTRACT

(+)-Discodermolide, a sponge-derived natural product, stabilizes microtubules more potently than paclitaxel despite the lack of any obvious structural similarities between the drugs. It competitively inhibits the binding of paclitaxel to tubulin polymers, hypernucleates microtubule assembly more potently than paclitaxel, and inhibits the growth of paclitaxel-resistant ovarian and colon carcinoma cells. Because paclitaxel shows clinical promise for breast cancer treatment, its effects in a series of human breast cancer cells were compared to those of (+)-discodermolide. Growth inhibition, cell and nuclear morphological, and electrophoretic and flow cytometric analyses were performed on (+)-discodermolide-treated MCF-7 and MDA-MB231 cells. (+)-Discodermolide potently inhibited the growth of both cell types (IC50 < 2.5 nM) at concentrations similar to those observed with paclitaxel. Complete inhibition of growth occurred with 10 nM or greater of each drug and was not reversed by removal. (+)-Discodermolide-treated cells exhibited condensed and highly fragmented nuclei. Flow cytometric comparison of cells treated with either drug at 10 nM, a concentration well below that achieved clinically with paclitaxel, showed both caused cell cycle perturbation and induction of a hypodiploid cell population. (+)-Discodermolide caused these effects more extensively and at earlier time points. The timing and type of high molecular weight DNA fragmentation induced by the two agents was consistent with induction of apoptosis. The results suggest that (+)-discodermolide has promise as a new chemotherapeutic agent against breast and other cancers.


Subject(s)
Alkanes , Antineoplastic Agents/therapeutic use , Breast Neoplasms/drug therapy , Carbamates , Lactones/therapeutic use , Paclitaxel/therapeutic use , Apoptosis , Breast Neoplasms/pathology , DNA Fragmentation , DNA, Neoplasm/drug effects , Diploidy , Female , Humans , Pyrones , Tumor Cells, Cultured/drug effects , Tumor Cells, Cultured/ultrastructure
15.
AIDS Res Hum Retroviruses ; 13(9): 743-50, 1997 Jun 10.
Article in English | MEDLINE | ID: mdl-9171218

ABSTRACT

Isolation of infectious molecular clones has been valuable to our understanding of HIV-1-induced pathogenesis. Two infectious molecular clones of HIV-1 were isolated longitudinally from a seropositive subject at different stages of the disease, using a standard bacteriophage lambda vector and a novel progressive amplification procedure. We found the progressive amplification procedure was simpler and more specific than the conventional plaque hybridization assay. The two infectious HIV-1 clones had distinct cell tropism and cytopathic properties. The HIV-1 clone obtained at the asymptomatic stage of the disease was macrophage tropic and had a non-syncytium-inducing property. In contrast, the HIV-1 clone obtained at the stage of AIDS development was dual tropic for T cells and macrophages and induced syncytia. A detailed analysis of the restriction sites of the two clones showed 9 of 21 sites to be unique. These unique restriction sites were predominantly localized in the envelope region. Furthermore, the nucleotide sequence analysis of the entire gp120 region supported the results from the restriction analysis and showed that these two clones are closely related, and the differences are restricted to the variable domains. The difference in amino acid sequences in the V3 region may explain the observed differences in T cell tropism and syncytium-inducing properties. Availability of two distinct infectious molecular clones from the same patient at different stages of the disease may be useful in studies on the mechanism of HIV-1 pathogenesis.


Subject(s)
Acquired Immunodeficiency Syndrome/virology , HIV Envelope Protein gp120/genetics , HIV Seropositivity/virology , HIV-1/classification , Acquired Immunodeficiency Syndrome/immunology , Acquired Immunodeficiency Syndrome/physiopathology , Adult , Amino Acid Sequence , Bacteriophage lambda , Cloning, Molecular , DNA, Viral/genetics , DNA, Viral/isolation & purification , Genetic Vectors , Giant Cells , HIV Envelope Protein gp120/chemistry , HIV Seropositivity/immunology , HIV Seropositivity/physiopathology , HIV-1/isolation & purification , HIV-1/pathogenicity , Humans , Longitudinal Studies , Lymphocytes/immunology , Lymphocytes/virology , Macrophages/virology , Male , Molecular Sequence Data , Phylogeny , Polymerase Chain Reaction/methods , Restriction Mapping , Sequence Alignment , T-Lymphocytes/virology , Time Factors
16.
Anticancer Res ; 17(3C): 1861-9, 1997.
Article in English | MEDLINE | ID: mdl-9216636

ABSTRACT

Z-1,1-dichloro-2,3-diphenylcyclopropane (a.k.a. Analog II, AII) is a known anti-breast cancer agent with apparent antiestrogenic effects and remarkably low toxicity in rodents. We have recently shown that AII and its major metabolite Z-alpha-chlorochalcone (ZCC) inhibit proliferation of both estrogen-responsive and -nonresponsive human breast cancer cells, suggesting its mechanism is not mediated by the type I estrogen receptor (ER). The present studies were performed to begin to define the molecular targets of AII and ZCC. Based on the compounds' structures and actions, we hypothesized that their effects could be due to interaction at type II estrogen binding sites (EBSII) and/or cellular microtubules. The affinities of AII ZCC and the positive control diethylstilbestrol (DES) for the ER (in MCF-7 and MCF-7/LY2 cells) and EBSII (in MCF-7, MCF 7/LY2, and MDA-MB231 cells) were determined with a whole cell assay for displacement of [3H]estradiol. The kinetics of their effects on cellular microtubules and cell cycle distribution of human breast cancer cells were measured by indirect immunofluorescence and flow cytometry. Their abilities to inhibit assembly of isolated tubulin in vitro were determined. AII, ZCC, and DES had similar affinities for the EBSII in the three cell lines. Neither AII nor ZCC displaced [3H]estradiol from the ER in MCF-7 cells, whereas DES did. The microtubule network of MDA-MB231 cells exposed to 100 microM AII or 10 microM ZCC began to disassemble within 1 hour of treatment and was completely diffuse after 6 hour of exposure to either drug. AII inhibited in vitro assembly of tubulin, with an IC50 of 6.7 +/- 0.9 microM, while ZCC was inactive below 40 microM. Both drugs caused accumulation of the cells in the G2/M phase of the cell cycle. The evidence suggests that the antitumor action of AII is mediated, at least in part, through the EBSII and/or perturbation of tubulin-microtubule dynamics. AII thus represents a new lead compound for design and discovery of novel antitumor agents directed against the EBSII and/or microtubules.


Subject(s)
Antineoplastic Agents/toxicity , Receptors, Estrogen/metabolism , Tamoxifen/analogs & derivatives , Tubulin/metabolism , Binding Sites , Binding, Competitive , Breast Neoplasms , Cell Cycle/drug effects , Chalcone/analogs & derivatives , Chalcone/toxicity , Chalcones , Diethylstilbestrol/toxicity , Estradiol/metabolism , Female , Fluorescent Antibody Technique, Indirect , Guanosine Triphosphate/metabolism , Humans , Microtubules/drug effects , Microtubules/ultrastructure , Tamoxifen/toxicity , Tubulin/drug effects , Tumor Cells, Cultured
17.
Opt Lett ; 22(5): 319-21, 1997 Mar 01.
Article in English | MEDLINE | ID: mdl-18183188

ABSTRACT

A laser model based on feedback produced by scattering has been developed to explain the narrow linewidth emission and input-output behavior observed in scattering gain media. The model is based on the transient two-level laser equations and includes the detailed spectral properties of the dye gain system. Monte Carlo methods were employed to calculate the threshold gain required for modeling the input-output and linewidth emission characteristics.

18.
AIDS Res Hum Retroviruses ; 12(9): 801-9, 1996 Jun 10.
Article in English | MEDLINE | ID: mdl-8738432

ABSTRACT

We analyzed sequence variability and function of the long terminal repeat (LTR) from syncytium-inducing (SI) and non-syncytium-inducing (NSI) HIV-1. Twenty LTR DNA clones were obtained by polymerase chain reaction amplification and molecular cloning from short-term cultures of SI and NSI viruses from an AIDS patient and two asymptomatic individuals, respectively. All the LTR clones tested contained multiple nucleotide changes (mostly G-to-A transitions), compared to the subtype B consensus sequence, which were clustered within the negative regulatory element, including NF-AT, USF, and TCF-1 alpha binding sites. The core promoter/TAR region sequences were highly conserved. The basal and Tat-mediated transcriptional activities of selected LTR clones tested were 0.1 to 1 and 0.2 to 0.5 times that of the control, respectively, regardless of the SI or NSI origin of the clones. Phylogenetic analysis revealed interi-solate sequence divergence in the LTR that was similar but not identical to previously analyzed vif sequences from the same samples. In particular, the inter-isolate distances from reference sequences differed for the LTR and vif. This raises the possibility that recombination occurred between corresponding LTR and vif loci of the quasi-species present in the isolates described here.


Subject(s)
DNA, Viral/genetics , Genes, vif , Giant Cells , HIV-1/genetics , Repetitive Sequences, Nucleic Acid , Acquired Immunodeficiency Syndrome/virology , Base Sequence , Binding Sites , Cloning, Molecular , DNA Mutational Analysis , Evolution, Molecular , Genetic Variation , HIV Infections/virology , HIV-1/isolation & purification , HIV-1/pathogenicity , Humans , Molecular Sequence Data , Point Mutation , Polymerase Chain Reaction , Recombination, Genetic , Regulatory Sequences, Nucleic Acid , Sequence Alignment , Sequence Homology, Nucleic Acid , Transcription Factors/metabolism , Transcription, Genetic
19.
J Gen Virol ; 77 ( Pt 5): 1083-8, 1996 May.
Article in English | MEDLINE | ID: mdl-8609474

ABSTRACT

The replicative properties of human immunodeficiency virus type 1 (HIV-1) isolates from asymptomatic carriers (asymptomatic isolates) and AIDS patients (AIDS isolates) were examined in the human T lymphocyte cell line H9. In agreement with earlier reports the replication of asymptomatic isolates was restricted whereas AIDS isolates replicate well in H9 cells. PCR analysis of H9 cells infected with asymptomatic isolates showed transient gag DNA synthesis for up to 48 h post-infection. This transient DNA synthesis was much lower than the amount of DNA synthesized by the AIDS isolates. The reduction in DNA synthesis reflects a restriction during virus entry. We further analysed transient DNA synthesis by the asymptomatic isolates to investigate possible post-entry restriction mechanisms. The transiently synthesized DNA was present only in the unintegrated form and was not transported in to the nucleus, suggesting an additional restriction mechanism for asymptomatic isolates in H9 cell lines at a step post-DNA synthesis and prior to or during nuclear translocation of newly synthesized viral DNA.


Subject(s)
HIV-1/growth & development , Homosexuality, Male , T-Lymphocytes/virology , Cell Line , DNA, Viral/analysis , DNA, Viral/biosynthesis , HIV Long Terminal Repeat , HIV-1/genetics , Humans , Male
20.
Opt Lett ; 21(4): 239-41, 1996 Feb 15.
Article in English | MEDLINE | ID: mdl-19865365

ABSTRACT

Intense isotropic laser emission from an optically pumped scattering gain medium has been used to induce isotropic lasing in an adjacent scattering gain medium at a longer wavelength. The energy-transfer mechanism between the media involved has been studied with a simple model based on radiation-transfer theory. The applications of this effect for wavelength-domain coding are also discussed.

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