Granular aluminium nanojunction fluxonium qubit.

Mesoscopic Josephson junctions, consisting of overlapping superconducting electrodes separated by a nanometre-thin oxide layer, provide a precious source of nonlinearity for superconducting quantum circuits. Here we show that in a fluxonium qubit, the role of the Josephson junction can also be played by a lithographically defined, self-structured granular aluminium nanojunction: a superconductor-insulator-superconductor Josephson junction obtained in a single-layer, zero-angle evaporation. The measured spectrum of the resulting qubit, which we nickname gralmonium, is indistinguishable from that of a standard fluxonium. Remarkably, the lack of a mesoscopic parallel plate capacitor gives rise to an intrinsically large granular aluminium nanojunction charging energy in the range of tens of gigahertz, comparable to its Josephson energy. We measure coherence times in the microsecond range and we observe spontaneous jumps of the value of the Josephson energy on timescales from milliseconds to days, which offers a powerful diagnostics tool for microscopic defects in superconducting materials.

Field-effect silicon-plasmonic photodetector for coherent T-wave reception.

Plasmonic internal photoemission detectors (PIPED) have recently been shown to combine compact footprint and high bandwidth with monolithic co-integration into silicon photonic circuits, thereby opening an attractive route towards optoelectronic generation and detection of waveforms in the sub-THz and THz frequency range, so-called T-waves. In this paper, we further expand the PIPED concept by introducing a metal-oxide-semiconductor (MOS) interface with an additional gate electrode that allows to control the carrier dynamics in the device and the degree of internal photoemission at the metal-semiconductor interfaces. We experimentally study the behavior of dedicated field-effect (FE-)PIPED test structures and develop a physical understanding of the underlying principles. We find that the THz down-conversion efficiency of FE-PIPED can be significantly increased when applying a gate potential. Building upon the improved understanding of the device physics, we further perform simulations and show that the gate field increases the carrier density in the conductive channel below the gate oxide to the extent that the device dynamics are determined by ultra-fast dielectric relaxation rather than by the carrier transit time. In this regime, the bandwidth can be increased to more than 1 THz. We believe that our experiments open a new path towards understanding the principles of internal photoemission in plasmonic structures, leading to PIPED-based optoelectronic signal processing systems with unprecedented bandwidth and efficiency.

Characterization of a submicro-X-ray fluorescence setup on the B16 beamline at Diamond Light Source.

An X-ray fluorescence setup has been tested on the B16 beamline at the Diamond Light Source synchrotron with two different excitation energies (12.7 and 17 keV). This setup allows the scanning of thin samples (thicknesses up to several micrometers) with a sub-micrometer resolution (beam size of 500 nm × 600 nm determined with a 50 µm Au wire). Sensitivities and detection limits reaching values of 249 counts s-1 fg-1 and 4 ag in 1000 s, respectively (for As Kα excited with 17 keV), are presented in order to demonstrate the capabilities of this setup. Sample measurements of a human bone and a single cell performed at B16 are presented in order to illustrate the suitability of the setup in biological applications.

A cross-sectional analysis of executive function in Down syndrome from 2 to 35 years.

BACKGROUND: Previous research has indicated a unique profile of executive function (EF) in children and adolescents with Down syndrome (DS). However, there is a paucity of research on EF in adults with DS. This study aimed to gain a broader understanding of strengths and weaknesses in EF in DS from 2 to 35 years. METHOD: Parents of 112 individuals with DS between 2 and 35 years participated in this study. Parents either completed the Behaviour Rating Inventory of Executive Function - for individuals 6+ years - or the Behaviour Rating Inventory of Executive Function Preschool Version - for children 2-5 years. RESULTS: Results suggest not only overall difficulties but also patterns of strength and weakness within EF for individuals with DS. For the 2 to 5-year-old group, emotional control and shift were relative strengths, planning/organisation and inhibit were intermediate skills, and working memory was a relative weakness. For the 6 to 18-year-old group, emotional control and organisation of materials were relative strengths, inhibit and initiate were intermediate skills, and working memory, monitor, planning/organisation, and shift were relative weaknesses. Most abilities were consistent from 2 to 18 years, except shift, which decreased in preadolescence before beginning to recover in adolescence. Across the full age range (2-35 years), composite scores indicated quadratic trends in inhibit, working memory, and planning/organisation, and a cubic trend in shift, with EF abilities generally declining in middle childhood before recovering in adulthood. CONCLUSIONS: This study extends previous research on EF in DS by providing an initial description of EF profiles across the lifespan. More longitudinal and behavioural research is needed to further characterise the development of EF in DS.

Missense mutation in the gene encoding the alpha subunit of rod transducin in the Nougaret form of congenital stationary night blindness.

Patients with congenital stationary night blindness enjoy normal daytime vision, which is mediated by cone photoreceptors, but are blind when ambient light is so dim that a normal individual would utilize only rod photoreceptors to see without colour discrimination. The disease is genetically heterogeneous. One form of dominantly inherited congenital night blindness is eponymously named "Nougaret' because pedigree analysis reveals that the disease originated in Jean Nougaret (1637-1719), a butcher who lived in Vendémian in southern France. Here we report that his affected descendants carry a missense mutation in the gene encoding the alpha subunit of rod transducin the G-protein that couples rhodopsin to cGMP-phosphodiesterase in the phototransduction cascade. Based on these results, rod transducin joins rhodopsin and the beta subunit of rod cGMP-phosphodiesterase to become the third component of the rod phototransduction cascade where a defect is implicated as a cause of stationary night blindness. Interestingly, the amino acid residue in transducin affected by the Nougaret mutation is in the position homologous to that affected by the oncogenic mutation originally reported in p21ras, a distant relative in the G-protein superfamily.

Purinergic modulation of preBötzinger complex inspiratory rhythm in rodents: the interaction between ATP and adenosine.

ATP signalling in the CNS is mediated by a three-part system comprising the actions of ATP (and ADP) at P2 receptors (P2Rs), adenosine (ADO) at P1 receptors (P1Rs), and ectonucleotidases that degrade ATP into ADO. ATP excites preBötzinger complex (preBötC) inspiratory rhythm-generating networks where its release attenuates the hypoxic depression of breathing. Its metabolite, ADO, inhibits breathing through unknown mechanisms that may involve the preBötC. Our objective is to understand the dynamics of this signalling system and its influence on preBötC networks. We show that the preBötC of mouse and rat is sensitive to P2Y(1) purinoceptor (P2Y(1)R) activation, responding with a >2-fold increase in frequency. Remarkably, the mouse preBötC is insensitive to ATP. Only after block of A(1) ADORs is the ATP-evoked, P2Y(1)R-mediated frequency increase observed. This demonstrates that ATP is rapidly degraded to ADO, which activates inhibitory A(1)Rs, counteracting the P2Y(1)R-mediated excitation. ADO sensitivity of mouse preBötC was confirmed by a frequency decrease that was absent in rat. Differential ectonucleotidase activities are likely to contribute to the negligible ATP sensitivity of mouse preBötC. Real-time PCR analysis of ectonucleotidase isoforms in preBötC punches revealed TNAP (degrades ATP to ADO) or ENTPDase2 (favours production of excitatory ADP) as the primary constituent in mouse and rat, respectively. These data further establish the sensitivity of this vital network to P2Y(1)R-mediated excitation, emphasizing that individual components of the three-part signalling system dramatically alter network responses to ATP. Data also suggest therapeutic potential may derive from methods that alter the ATP-ADO balance to favour the excitatory actions of ATP.

Low dose novel PARP-PI3K inhibition via nanoformulation improves colorectal cancer immunoradiotherapy.

Multimodal therapy is often used in oncology to overcome dosing limitations and chemoresistance. Recently, combination immunoradiotherapy has shown great promise in a select subset of patients with colorectal cancer (CRC). Furthermore, molecularly targeted agents delivered in tandem with immunotherapy regimens have been suggested to improve treatment outcomes and expand the population of responding patients. In this study, radiation-sensitizing small molecules niraparib (PARP inhibitor) and HS-173 (PI3K inhibitor) are identified as a novel combination that synergistically enhance toxicity and induce immunogenic cell death both in vitro and in vivo in a CRC model. These inhibitors were co-encapsulated in a polymer micelle to overcome solubility limitations while minimizing off-target toxicity. Mice bearing syngeneic colorectal tumors (CT26) were administered these therapeutic micelles in combination with X-ray irradiation and anti-CTLA-4 immunotherapy. This combination led to enhanced efficacy demonstrated by improved tumor control and increased tumor infiltrating lymphocytes. This report represents the first investigation of DNA damage repair inhibition combined with radiation to potentiate anti-CTLA-4 immunotherapy in a CRC model.

Post-tooth extraction sepsis without locoregional infection--a population-based study in Taiwan.

OBJECTIVE: To investigate the incidence and risk factors of post-tooth extraction sepsis in patients without locoregional infection. SUBJECTS AND METHODS: We assessed all claim records of the Taiwanese National Health Insurance program in 2005. Admissions for patients aged > or =16 years containing a discharge diagnosis of sepsis, and who received tooth extraction within 14 days before the admission were identified. Patient charts were reviewed to confirm the diagnosis of sepsis and rule out other infection sources. The relationship between postextraction sepsis (PES) and clinical parameters was analyzed. RESULTS: Thirty-three of the 2 223 971 extraction cases met the criteria of PES, an incidence of 1.48 per 100 000, and seven patients (21.2%) died of the disease. Aging significantly increased the risk of PES (P < 0.001). Pre-existing comorbidities were found in 20 of the 33 cases, with diabetes mellitus and hematologic diseases the most common. The method, number, and position of extraction had no influence on PES incidence. Blood cultures were positive in 25 patients (75.8%) and isolates included species of the Streptococcus, Actinomyces, Klebsiella, Bacteroides, Prevotella, and Enterococcus genera. CONCLUSION: Tooth extraction is associated with a low but significant risk of postoperative sepsis, especially in the elderly and patients with underlying diseases.

Cell-mediated immunity and head and neck cancer: with special emphasis on betel quid chewing habit.

Betel quid (BQ) chewing is popular in Taiwan, India, and many southeast-Asian countries. BQ chewing has strong association with the risk of oral leukoplakia (OL), oral submucous fibrosis (OSF), and oral cancer (OC). BQ components exhibit genotoxicity and may alter the structure of DNA, proteins and lipids, resulting in production of antigenicity. BQ ingredients are also shown to induce keratinocyte inflammation by stimulating the production of prostaglandins, TNF-alpha, IL-6, IL-8, and granulocyte-macrophage colony-stimulating factor (GM-CSF) in keratinocytes. These events may provoke tissue inflammation, early cell-mediated immunity (CMI), and immune surveillance in BQ chewers. However, BQ components also directly affect the functional activities of immunocompotent cells, and moreover tumor cells may hypo-respond to the CMI via diverse mechanisms such as induction of apoptosis of lymphocytes, induction of production of suppressor T cells, downregulation of MHC molecules in tumor cells, etc. Clinically, an alteration in lymphocyte subsets, a decrease in total number of lymphocytes, and a reduction in functional activities of CMI have been observed in isolated peripheral blood mononuclear cells (PBMC) and tumor infiltrated lymphocytes (TIL) in patients with OSF, OL or OC. Adaptation of tumor cells to immune system may promote clonal selection of resistant tumor cells, leading to immune tolerance. Future studies on effects of BQ components on CMI and humoral immunity in vitro and in vivo can be helpful for chemoprevention of BQ-related oral mucosal diseases. To elucidate how virus infection, tobacco, alcohol and BQ consumption, and other environmental exposure affect the immune status of patients with oral premalignant lesions or OC will help us to understand the immunopathogenesis of OC and to develop immunotherapeutic strategies for OC.

Trends in prevalence of diabetes mellitus in patients with myocardial infarction and effect of diabetes on survival. The Minnesota Heart Survey.

OBJECTIVE: The purpose of this study was to document trends in the prevalence of diabetes among men and women hospitalized for myocardial infarction (MI) and to determine the effect of diabetes on in-hospital case fatality rates and long-term survival. RESEARCH DESIGN AND METHODS: The Minnesota Heart Survey is a population-based surveillance system that has monitored trends in coronary heart disease morbidity since 1970. As part of this effort, a 50% random sample of acute MI discharge records in Minneapolis-St. Paul metropolitan area hospitals was abstracted in 1970, 1980, and 1985. RESULTS: The prevalence of diabetes among MI patients was compared over time, and the data indicated a significant increase between 1970 and 1985 in both men (8.2 vs. 16.8%, P less than 0.001) and women (16.0 vs. 25.8%, P = 0.01). Diabetic individuals had an odds ratio of in-hospital death after an MI 1.5 times that of nondiabetic individuals (P less than 0.01) after controlling for the effects of sex, age, and year of MI. Among discharged MI survivors, the risk of death was 40% higher (P less than 0.01) in diabetic individuals than nondiabetic individuals after 6 yr of follow-up. Compared with nondiabetic individuals, diabetic individuals appeared more likely to have cardiac (pump) failure with acute MI. CONCLUSIONS: Our findings suggest that the risk of coronary heart disease morbidity and mortality attributable to diabetes may be increasing over time. Therefore, clinicians need to take extra care in the management of MIs in diabetic individuals, and public health efforts to reduce diabetes prevalence are warranted.

Estrogen replacement therapy decreases hyperandrogenicity and improves glucose homeostasis and plasma lipids in postmenopausal women with noninsulin-dependent diabetes mellitus.

Hyperandrogenicity in women is closely associated with insulin resistance and a risk factor for cardiovascular disease and noninsulin-dependent diabetes mellitus (NIDDM). Therefore, 25 postmenopausal women with NIDDM and sex hormone-binding globulin values less than 60 nmol/L, as an indicator of a moderate hyperandrogenicity, were treated with 2 mg 17-beta-estradiol orally for 3 months in a double-blind, cross-over, placebo-controlled trial. During the last 16 days of active treatment, 1 mg norethisterone acetate was added for 10 days for endometrial protection. Blood glucose, glycosylated hemoglobin, insulin, c-peptide, lipoprotein profile, sex steroid hormones, GH, and insulin-like growth factor I (IGF-I) were measured, and insulin sensitivity was determined by the euglycemic hyperinsulinemic clamp method. All metabolic measurements were taken at baseline and after 68 days of active or placebo treatment. Estradiol treatment, compared with the placebo period, was followed by a marked increase of sex hormone-binding globulin and a decrease of free testosterone. Blood glucose, glycosylated hemoglobin, c-peptide, total cholesterol, low-density lipoprotein cholesterol, and IGF-I decreased significantly (P < 0.01-P < 0.001), whereas high-density lipoprotein cholesterol rose (P < 0.001). In conclusion, estrogen replacement therapy in postmenopausal women with NIDDM ameliorated hyperandrogenicity, and this was accompanied by marked improvements in glucose homeostasis and lipoprotein profile.

Low rate of Rhesus immunization from Rh-incompatible blood transfusions during liver and heart transplant surgery.

Transfusion of one unit or more of Rh-positive red blood cells normally causes circulating anti-D antibody to appear 2-6 months later in 80-95% of Rh- persons. We asked whether transplant immunosuppression with cyclosporine and corticosteroids affects Rh immunization. Nineteen Rh- liver, heart, and heart-lung transplant recipients received 3-153 (median: 10) units of Rh+ RBCs at surgery and were tested for anti-D greater than 2 months later. Three patients developed anti-D at 11-15 days; one may have had an unusually rapid primary immune response and two were secondary to previous exposure by pregnancy. None of the other 16 patients had anti-D when tested 2.5-51 months later (13 patients, greater than 11.5 months). This low rate of Rhesus immunization in association with cyclosporine immunosuppression allows greater flexibility in meeting the transfusion needs of Rh- liver and heart transplant patients. Caution is still advised in young females and in patients who may have been previously exposed to Rh+ RBCs by transfusion or by pregnancy prior to the availability of perinatal Rh immune globulin twenty years ago. Other humoral immune responses to some vaccines or infectious agents may also be impaired in transplant patients.

Automatic three-dimensional multimodality registration using radionuclide transmission CT attenuation maps: a phantom study.

UNLABELLED: Coregistration of images from a single subject, acquired by different modalities, is important in clinical diagnosis, surgery and therapy planning. The purpose of this study was to evaluate, using a physical torso phantom, a novel, fully automated method for three-dimensional image registration of CT and SPECT, using radionuclide transmission (RNT) attenuation maps. METHODS: We obtained CT scans and SPECT scans paired with RNT maps of an anthropomorphic cardiac phantom. RNT attenuation maps were acquired using an uncollimated 99mTc-filled flood source. RNT and SPECT scans were acquired in the same spatial orientation (usual clinical practice in nonuniform attenuation correction). In addition, CT attenuation maps (CTMAPs) for 99mTc SPECT were generated from CT by linear energy scaling. RNT maps were registered to CT and CTMAPs by iterative simplex minimization of count difference and uniformity index (sum of RNT map intensity variances corresponding to each intensity level in the CT volume). In each iteration, three shifts and three angles were adjusted. To register SPECT to CT, we applied the RNT transformation parameters to SPECT. RESULTS: RNT maps could be registered to CT and CTMAP images using both criteria. The average three-dimensional distance between landmark and automated registration was 2.5 +/- 1.2 mm for count difference and 3.3 +/- 1.3 mm for uniformity index. The three-dimensional reproducibility errors were 1.2 +/- 0.7 mm for count difference, 2.1 +/- 0.5 mm for uniformity index and 2.3 +/- 1.0 mm for manual marker registration. The minimization of uniformity index was robust when up to 50% CT or RNT slices were missing and was not affected significantly (<2 mm) by realistic variation in CT values (+/- 12 Hounsfield units). CONCLUSION: In addition to typical use in nonuniform attenuation correction, RNT maps can be used for fully automated three-dimensional registration of SPECT to CT. Such registration is not affected by features and quality of SPECT images and avoids difficulties associated with fiducial markers. Our method can be applied to SPECT-CT registration of various organs, such as brain, heart, lungs, breasts and abdomen, including oncological scans.

Nonisotropic attenuation in SPECT: phantom tests of quantitative effects and compensation techniques.

A quantitative study of nonisotropic attenuation in SPECT imaging is presented. The study includes a case where the spatial distribution of the attenuation coefficient is nonuniform, as well as a case where the photon path length in the attenuating medium is variable as a function of direction. The effects are studied using phantoms with known source activity and density distributions. Reconstructed images of the phantoms with and without attenuation compensation are compared with the source distribution. Three methods are used to provide partial attenuation compensation, using effective attenuation coefficients. These coefficients include some of the effects of photon scatter, but scatter is not explicitly treated. One attenuation compensation method involves a multiplicative postprocessing correction using an assumed constant attenuation coefficient. A modification of this technique is implemented using the correct nonuniform attenuation map to determine the multiplication factors. A single-iteration technique is used to provide a more complete compensation. The results indicate that nonuniform attenuation can produce significant distortion in line spread functions and in larger distributed sources. This distortion can alter volume determinations, quantitation measurements, and the shape of small objects, and can cause misplacement of counts into regions of low density. The distortion cannot be eliminated by the multiplicative postprocessing correction, but the single-iteration technique can significantly decrease the distortion.

Evaluation of the gene encoding the gamma subunit of rod phosphodiesterase in retinitis pigmentosa.

PURPOSE: To determine whether defects in the gene encoding the gamma subunit of rod cyclic guanosine monophosphate-phosphodiesterase (PDE-g) cause some form of hereditary retinal degeneration or dysfunction. METHODS: A restriction map, an intron/exon map, and a partial sequence of the human genomic locus corresponding to this gene were ascertained. Based on this information, the single-strand conformation polymorphism technique (SSCP) was used to screen the coding region as well as most splice donor and acceptor sites for mutations in a total of 704 unrelated patients with retinitis pigmentosa, Usher's syndrome type I or type II, Leber's congenital amaurosis, the Laurence-Moon-Bardet-Biedl syndrome, or other hereditary retinal disease. RESULTS: Two frequent polymorphisms were found, as well as three rare sequence variations, none of which correlated with any phenotype examined. CONCLUSIONS: In view of these negative results and those of a previously published negative Southern blot analysis of an overlapping set of patients, it is unlikely that mutations in the PDE-g gene are a common cause of any of the forms of retinal degeneration or dysfunction so far examined.

Dominant and digenic mutations in the peripherin/RDS and ROM1 genes in retinitis pigmentosa.

PURPOSE: To measure the proportion of cases of retinitis pigmentosa (RP) caused by mutations in the peripherin/RDS (RDS) and ROM1 genes. METHODS: The single-strand conformation polymorphism (SSCP) method was used to analyze 227 unrelated patients with dominant or recessive RP for mutations in the RDS gene and an overlapping set of 315 unrelated patients for mutations in the ROM1 gene (excluding patients with other known RP genes). Variant bands revealed by SSCP were studied further by polymerase chain reaction-based, direct genomic sequencing and, where possible, by cosegregation analysis in the families of the index cases. RESULTS: Four index patients were found to have RP as a result of one of four dominant mutations in the RDS gene, two of which are novel. Four other index patients were found to have digenic RP as a result of the combination of heterozygous mutations in both the RDS and the ROM1 gene, with one of the ROM1 mutations being novel. The digenic cases all had the same RDS mutation (the missense change Leu185Pro), but each had one of three different ROM1 mutations. The authors were unable to determine through cosegregation analysis whether three other changes encountered in the RDS gene and five in the ROM1 gene were pathogenic. CONCLUSIONS: The authors found mutations in the RDS gene as a cause of dominant or digenic RP and mutations in the ROM1 gene as a cause of digenic RP. No cases of RP caused by ROM1 mutations alone have been discovered thus far. Mutations in the RDS and ROM1 genes are infrequent causes of RP, together accounting for only a few percent of patients in the United States and Canada.

Low incidence of retinitis pigmentosa among heterozygous carriers of a specific rhodopsin splice site mutation.

PURPOSE: To determine whether a rhodopsin splice donor site mutation at the 5' end of intron 4 is a cause of autosomal dominant retinitis pigmentosa. METHODS: Heterozygous carriers of the same rhodopsin splice site mutation in two pedigrees were identified using single-strand conformation polymorphism analysis. Twelve heterozygous carriers were evaluated by ophthalmoscopy. Goldmann kinetic visual fields, dark adaptation thresholds, and full-field electroretinograms including rod intensity-response functions. Clinical findings from the heterozygous carriers of the splice site mutation were compared with those from heterozygous carriers from a separate family with a known recessive rhodopsin null mutation, Glu249X. RESULTS: Analysis of DNA from 48 members of two pedigrees revealed 25 heterozygous carriers of the splice site mutation, ranging in age from 14 to 82 years. There were no homozygotes with the rhodopsin splice site mutation. Of the 25 heterozygous carriers, 24 were asymptomatic. Eleven asymptomatic heterozygotes were examined, including four older than 65 years of age. They were found to have normal fundi, full visual fields, and slightly elevated final rod dark adaptation thresholds. Their rod electroretinographic b-wave amplitudes were slightly diminished over the full range of blue light intensities. Rod a-wave implicit times were slightly but significantly prolonged in response to the brightest blue flash of light. These subtle abnormalities in rod function were similar to those found in asymptomatic heterozygous carriers of the recessive Glu249X mutation. Only one of the 25 heterozygous carriers of the splice site mutation had symptoms and signs of retinitis pigmentosa. CONCLUSIONS: Because 96% of these heterozygous carriers do not have retinitis pigmentosa, it is unlikely that this mutation in intron 4 is a dominant allele. The subtle abnormalities of rod function found in asymptomatic carriers are similar to those found in heterozygous carriers of a recessive rhodopsin allele. The one heterozygous carrier with retinitis pigmentosa probably has a second mutation in the rhodopsin gene or has a defect or defects in another gene that causes his disease.

Inducing the cell cycle arrest and apoptosis of oral KB carcinoma cells by hydroxychavicol: roles of glutathione and reactive oxygen species.

Hydroxychavicol (HC; 10 - 50 microM), a betel leaf component, was found to suppress the 2% H(2)O(2)-induced lucigenin chemiluminescence for 53 - 75%. HC (0.02 - 2 microM) was also able to trap superoxide radicals generated by a xanthine/xanthine oxidase system with 38 - 94% of inhibition. Hydroxyl radicals-induced PUC18 plasmid DNA breaks was prevented by HC (1.6 - 16 microM). A 24-h exposure of KB cells to HC (0.5, 1 mM) resulted in 54 - 74% cell death as analysed by a 3-(4,5-dimethyl-thiazol-2-yl)-2,5-diphenyl-tetrazolium bromide (MTT) assay. HC (10, 50 microM) further suppressed the growth of KB cells (15 and 76%, respectively). Long-term colony formation of KB cells was inhibited by 51% with 10 microM HC. Pretreatment of KB cells with 100 microM HC inhibited the attachment of KB cells to type I collagen and fibronectin by 59 and 29%, respectively. Exposure of KB cells to 0.1 mM HC for 24 h resulted in cell cycle arrest at late S and G2/M phase. Increasing the HC concentration to 0.25 and 0.5 mM led to apoptosis as revealed by detection of sub-G(0)/G(1) peaks with a concomitant decrease in the number of cells residing in late S and G(2)/M phase. Inducing the apoptosis of KB cells by HC was accompanied by marked depletion in reduced form of GSH (>0.2 mM) and the increasing of reactive oxygen species production (>0.1 mM) as analysed by CMF- and DCF-single cell fluorescence flow cytometry. These results indicate that HC exerts antioxidant property at low concentration. HC also inhibits the growth, adhesion and cell cycle progression of KB cells, whereas its induction of KB cell apoptosis (HC>0.1 mM) was accompanied by cellular redox changes.