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PubMed2003

Characterization and chromosomal instability of novel derived cell lines from a wt-erbB-2 transgenic mouse model.

Amplification and overexpression of the erbB-2 (HER-2/neu) proto-oncogene and exposure to the cell cycle mitogenic hormone estrogen (E2) have been associated with mammary tumorigenesis. Phytoestrogens found in soy act as selective estrogen receptor modulators and may also modify mammary carcinogenesis. We have used the wt-erbB-2 transgenic mouse model to study the effects of estrogen and dietary phytoestrogens on erbB-2-associated mammary tumorigenesis. Transgenic mice were treated with short-term E2 or placebo pellets during the early reproductive period and fed a casein or soy diet for life. Mammary tumors from the different treatment groups were used for the derivation of novel cell lines. Comparative genomic hybridization (CGH), flow cytometry, assays of cell proliferation and soft agar cloning were performed to study genomic instability and in vitro characteristics. CGH data were compared with corresponding parental tumors. Mammary tumors exhibited significantly fewer genetic changes than cell lines by CGH. Cell lines from soy-fed animals (that developed tumors with a longer latency) demonstrated the greatest frequency of chromosomal gain and loss. The E2-treated, casein-fed animals (that developed tumors with the shortest latency) had the fewest genetic changes in derived lines by CGH. Nonetheless, E2-associated tumors in vivo and lines in vitro had the most aggressive phenotypes. In addition, over 40% of all derived cell lines, and both tumors from the placebo-treated casein-fed mice, exhibited loss of chromosome 4 by CGH. In aggregate, our data suggest that estrogenic signaling influences mammary tumor development in this transgenic mouse model bearing the rat wt-erbB-2 gene. Once induced, tumors and derived lines demonstrate persistent phenotypic characteristics, including tumor aggression and shortened latency in E2-treated mice. Loss of chromosome 4 was commonly identified in derived lines and may have facilitated immortalization or passage in culture.

Animals↗

PubMed1997

Effects of serotonin on platelet activation in whole blood.

Serotonin (5-hydrotryptamine, 5-HT) is a weak platelet agonist, which has not been evaluated fully with respect to platelet responses in whole blood. We thus re-evaluated platelet responses to 5-HT using three whole blood techniques: flow cytometry, impedance aggregometry and filtragometry. At concentrations up to 10(-5) mol/l, 5-HT per se failed to induce platelet aggregation in whole blood, or to increase platelet fibrinogen binding or P-selectin expression. However, 5-HT potentiated platelet responses to low concentrations of adenosine diphosphate (ADP) or thrombin dose-dependently. 5-HT (10(-7), 10(-6) and 10(-5) mol/l) increased ADP-induced platelet fibrinogen binding by 40, 59 and 79%, while P-selectin expression increased by 45, 64 and 95%, respectively (P < 0.05; n = 10). The enhancing effects of 5-HT were even more pronounced in thrombin-stimulated samples, as 5-HT at 10(-8), 10(-7), 10(-6) and 10(-5) mol/l increased fibrinogen binding by 56, 128, 212 and 260% (P < 0.05), and P-selectin expression by 31, 56, 89 and 109%, respectively (P < 0.01; n = 10). The response to 5-HT was inhibited dose-dependently by a highly selective 5-HT2A receptor antagonist (SR 46349), with almost complete inhibition at 10(-6) mol/l. Impedance aggregometry showed a significant enhancement in 5 x 10(-6) mol/l ADP-induced platelet aggregation caused by 5-HT at 8 x 10(-8) mol/l (from 7.58 +/- 2.50 omega to 9.02 +/- 2.43 omega, P < 0.02, n = 12). Similarly, filtragometry readings, i.e. the time taken for platelet aggregates to occlude a microfilter, were shortened by 27% (P < 0.05, n = 9), reflecting increased platelet aggregability. Our data suggest that 5-HT per se does not activate platelets, but dose-dependently enhances platelet activation induced by ADP and, in particular, thrombin in whole blood. Thus, the idea that 5-HT is a 'helper agonist' is supported; this effect is mediated by 5-HT2A receptors.

Adenosine Diphosphate↗

PubMed1999

Spread of HIV infection in a rural area of Tanzania.

OBJECTIVE: To assess the spread of HIV into rural areas. METHODS: Since 1994 a demographic surveillance system (with 5-monthly rounds) and open adult cohort study have been established in a rural ward in Tanzania. Two sero-surveys of all resident adults aged 15-44 and 15-46 years were conducted in 1994 1995 and 1996-1997 respectively. Qualitative data were collected on mobility, bars and commercial sex. RESULTS: Attendance of the two rounds of survey was 5820 (78%) and 6413 (80%) in 1994/1995 and 1996/1997 respectively. HIV prevalence increased from 5.8% to 6.6%. HIV incidence was 0.73 and 0.84 per 100 person years among men and women respectively. HIV incidence under the age of 20 years was low among both sexes. Striking differences in HIV prevalence and incidence were observed within the small geographic area studied: HIV prevalence in the trading center was twice that in the area surrounding the trading center (within 2 km) and three to four times that in the rural villages (within 8 km of the trading center). Aggregate level data showed significant differences between the trading center and nearby rural villages in terms of sexual behavior, commercial sex workers, mobility of the population, and alcohol use. CONCLUSION: This study documents the existence of very substantial HIV prevalence and incidence differences within a small geographic rural area. The rapid decrease in HIV prevalence within a small rural area emphasizes the importance of concentrating HIV prevention efforts on high transmission areas, such as trading centers, especially in resource-poor settings. Furthermore, this has considerable implications for monitoring the spread of HIV through sentinel sites, as such sites are typically located in high transmission areas.

Adolescent↗

PubMed1998

Characteristics of a low affinity passive Ca2+ influx component in rat parotid gland basolateral plasma membrane vesicles.

We have previously reported the presence of two Ca2+ influx components with relatively high (KCa = 152 +/- 79 microM) and low (KCa = 2.4 +/- 0.9 mM) affinities for Ca2+ in internal Ca2+ pool-depleted rat parotid acinar cells [Chauthaiwale et al. (1996) Pfluegers Arch. 432: 105-111]. We have also reported the presence of a high affinity Ca2+ influx component with KCa = 279 +/- 43 microM in rat parotid gland basolateral plasma membrane vesicles (BLMV). [Lockwich, Kim & Ambudkar (1994) J. Membrane Biol. 141:289-296]. The present studies show that a low affinity Ca2+ influx component is also present in BLMV with KCa = 2.3 +/- 0.41 mM (Vmax = 16.36 +/- 4.11 nmoles of Ca2+/mg protein/min). Our data demonstrate that this low affinity component is similar to the low affinity Ca2+ influx component that is activated by internal Ca2+ store depletion in dispersed parotid gland acini by the following criteria: (i) similar KCa for calcium flux, (ii) similar IC50 for inhibition by Ni2+ and Zn2+; (iii) increase in KCa at high external K+, (iv) similar effects of external pH. The high affinity Ca2+ influx in cells is different from the low affinity Ca2+ influx component cells in its sensitivity to pH, KCl, Zn2+ and Ni2+. The low and high affinity Ca2+ influx components in BLMV can also be distinguished from each other based on the effects of Zn2+, Ni2+, KCl, and dicyclohexylcarbodiimide. In aggregate, these data demonstrate the presence of a low affinity passive Ca2+ influx pathway in BLMV which displays characteristics similar to the low affinity Ca2+ influx component detected in parotid acinar cells following internal Ca2+ store depletion.

Animals↗

PubMed2025

Estimating population structure using epigenome-wide methylation data.

INTRODUCTION: In epigenome-wide association analysis (EWAS), unaddressed population stratification often leads to inflation. We aimed to compute methylation population scores (MPSs) that predict genetic principal components (GPCs) using a feature selection and regression approach. METHODS: We used multi-ethnic methylation data (Illumina 450K/EPIC array) from unrelated MESA (n=929), CARDIA (n=1123), JHS (n=1365), ARIC (n=2338), and HCHS/SOL (n=1475) individuals, randomly assigning 85% of participants from each cohort to a training dataset and the remaining 15% to a test dataset. First, we estimated the associations of GPCs with each available CpG methylation site using linear regression within each cohort, adjusting for age, sex, smoking status, race/ethnic background (as a proxy for background information associated with lifestyle and other environmental exposures that may impact methylation), alcohol use status, body mass index, and cell type proportions. We meta-analyzed the associations across cohorts and selected CpG sites with association FDR-adjusted q-value <0.05. We next aggregated individuallevel data across the cohort-specific training datasets, and applied two-stage weighted least squares Lasso regression, with the GPCs as the outcomes and the selected CpG sites as penalized predictors, adjusting for the aforementioned covariates. The developed MPSs are the weighted sum of selected CpG sites from the Lasso. To evaluate the developed MPSs, we constructed them in the test dataset, and compared them with GPCs, and with MPSs constructed based on a previously-published paper. Comparison was based on correlation analysis and data visualization. We demonstrate the use of the MPSs in EWAS. RESULTS: In the test dataset, the MPSs were highly correlated with GPCs, with correlation decreasing, though not monotonically, for later components. Specifically, MPS1 and GPC1 had R2= 0.99, while MPS7 and GPC7 had R2=0.27 (the lowest observed correlation). In data visualization, MPSs had similar patterns as GPCs in differentiating self-reported White, Black, and Hispanic/Latino groups, while outperforming MPC constructed using alternative published methods. MPSs showed comparable performance to GPCs in reducing some of the inflation in EWAS. CONCLUSIONS: Methylation-based population scores provide a reliable estimate of population structure in the data and can complement GPCs when genetic data are absent. Unlike previous methods based on unsupervised methylation PCA, MPSs uses supervised learning with covariate adjustment to capture genetic structure across diverse populations. The weights for each GPCs derived in our study can be applied to generate MPSs in other studies.

Journal Article↗

PubMed1985

Changes in the platelet membrane glycoprotein IIb.IIIa complex during platelet activation.

Platelet activation is accompanied by the appearance on the platelet surface of approximately 45,000 receptor sites for fibrinogen. The binding of fibrinogen to these receptors is required for platelet aggregation. Although it is established that the fibrinogen receptor is localized to a heterodimer complex of the membrane glycoproteins, IIb and IIIa, little is known about the changes in this complex during platelet activation that result in the expression of the receptor. In the present studies, we have developed and characterized a murine monoclonal anti-platelet antibody, designated PAC-1, that binds to activated platelets, but not to unstimulated platelets. PAC-1 is a pentameric IgM that binds to agonist-stimulated platelets with an apparent Kd of 5 nM. Binding to platelets is dependent on extracellular Ca2+ (KCa = 0.4 microM) but is not dependent on platelet secretion. Platelets stimulated with ADP or epinephrine bind 10,000-15,000 125I-PAC-1 molecules/platelet while platelets stimulated with thrombin bind 20,000-25,000 molecules/platelet. Several lines of evidence indicate that PAC-1 is specific for the glycoprotein IIb.IIIa complex. First, PAC-1 binds specifically to the IIb.IIIa complex on Western blots. Second, PAC-1 does not bind to thrombasthenic platelets or to platelets preincubated with ethylene glycol bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid at 37 degrees C, both of which lack the intact IIb.IIIa complex. Third, PAC-1 competitively inhibits the binding of 125I-A2A9, and IgG monoclonal antibody that is specific for the IIb.IIIa complex. Fourth, the antibody inhibits fibrinogen-mediated platelet aggregation. These data demonstrate that PAC-1 recognizes an epitope on the IIb.IIIa complex that is located near the platelet fibrinogen receptor. Platelet activation appears to cause a Ca2+-dependent change involving the glycoprotein IIb.IIIa complex that exposes the fibrinogen receptor and, at the same time, the epitope for PAC-1.

Antibodies, Monoclonal↗

PubMed1995

Medicare payments from diagnosis to death for elderly cancer patients by stage at diagnosis.

Although extensive resources go to cancer care, national population-based data on the costs of such care at the patient level have been unavailable. Medicare payments subsequent to diagnosis of cancer for elderly enrollees with five common cancers were estimated using tumor registry data from the Surveillance, Epidemiology, and End Results Program linked to Medicare claims from 1984 to 1990. The time between diagnosis and death was divided into four phases corresponding to the clinical course of solid tumors, average payments for each phase were estimated (including payments for services not related to cancer), then phase-specific payment data were aggregated. Average payments by phase varied among cancer sites, especially in the initial care phase, where payments were highest for lung and colorectal cancers ($17,500 in 1990 dollars) and lowest for female breast cancer ($8,913). Total Medicare payments from diagnosis to death were highest for persons with bladder cancer ($57,629) and lowest for those with lung cancer ($29,184). Low payments for persons with lung cancer corresponded to brief survival times. Persons diagnosed at earlier stages incurred higher total payments between diagnosis and death than those diagnosed at later stages, reflecting their longer survival. This implies that early detection may increase total Medicare expenditures by extending beneficiaries' lives. However, Medicare payments per year of survival were lower for earlier stages. Data on Medicare payments subsequent to diagnosis of cancer are useful for identifying the cost implications of differences in treatment patterns by demographic characteristics, geography, and delivery systems; comparing the financial impact of alternative therapies; evaluating the long-term cost impacts of screening and prevention programs; and risk-adjusting payments to health plans.

Aged↗

PubMed1989

Prevention of platelet aggregation by dietary polyunsaturated fatty acids in the biodegradable polyurethane vascular prosthesis: an experimental model in pigs.

A 6-7 cm long degradable polyurethane vascular prosthesis was implanted in the infrarenal aorta of 25 young growing pigs, sacrificed from day 30 to 365 to study the processes of degradation and tissue growth, the characteristics of prosthetic substitutes and the incidence of thrombosis. Ten animals were used as controls and 15 were fed with cod liver oil (25 ml twice daily). Aortography performed at day 30, 60 and 90 showed 100% thrombosed implants in the controls, while in the lipid diet fed animals there was 100% patency. At graft retrieval, there were 7 patent grafts out of 9 in the cod liver oil fed animals. Laboratory tests indicated that the lipid diet rich in n-3 polyunsaturated fatty acids induces significant modifications of lipid metabolism preventing platelet aggregation. These data correlate well with findings of the morphological studies showing that all patent prostheses are lined with tissues similar to the endothelium of the native aorta with a mid layer made of circular and longitudinal smooth muscle cells well differentiated at day 180. These data show that the essential polyunsaturated fatty acid rich diet is able to prevent thrombosis of the biodegradable polyurethane vascular prosthesis. The combination of a synthetic material and the lipid diet experimental model, makes it possible to assess the long-term tissue-synthetic material interaction and the process of tissue growth.

Animals↗

PubMed2002

Antibiotic prescription practices, consumption and bacterial resistance in a cross section of Swedish intensive care units.

BACKGROUND: The purpose of this work was to study usage of antibiotics, its possible determinants, and patterns of bacterial resistance in Swedish intensive care units (ICUs). METHODS: Prospectively collected data on species and antibiotic resistance of clinical isolates and antibiotic consumption specific to each ICU in 1999 were analyzed together with answers to a questionnaire. Antibiotic usage was measured as defined daily doses per 1000 occupied bed days (DDD1000). RESULTS: Data were obtained for 38 ICUs providing services to a population of approximately 6 million. The median antibiotic consumption was 1257 DDD1000 (range 584-2415) and correlated with the length of stay but not with the illness severity score or the ICU category. Antibiotic consumption was higher in the ICUs lacking bedside devices for hand disinfection (2193 vs. 1214 DDD1000, p=0.05). In the ICUs with a specialist in infectious diseases responsible for antibiotic treatment the consumption pattern was different only for use of glycopeptides (58% lower usage than in other ICUs: 26 vs. 11 DDD1000,P=0.02). Only 21% of the ICUs had a written guideline on the use of antibiotics, 57% received information on antibiotic usage at least every 3 months and 22% received aggregated resistance data annually. Clinically significant antimicrobial resistance was found among Enterbacter spp. to cephalosporins and among Enterococcus spp. to ampicillin. CONCLUSIONS: Availability of hand disinfection equipment at each bed and a specialist in infectious diseases responsible for antibiotic treatment were factors that correlated with lower antibiotic consumption in Swedish ICUs, whereas patient-related factors were not associated with antibiotic usage.

Adult↗

PubMed1993

Orthovanadate induces translocation of phospholipase C-gamma 1 and -gamma 2 in permeabilized mast cells.

Rapid activation of phospholipase C (PLC) with a resultant increase in phosphatidylinositol hydrolysis occurs after aggregation of the high affinity receptor for IgE (Fc epsilon RI) on the surface of mast cells. We previously described an increase in PLC activity associated with the particulate fraction of rat basophilic leukemia (RBL) cells after Fc epsilon RI aggregation, and this redistribution of enzyme activity correlated with an increase in immunoreactivity of the gamma 1 isozyme of PLC in the particulate fraction by Western blot analysis (J. Immunol. 148:2194-2200, 1992). We now report that the tyrosine phosphatase inhibitor orthovanadate mimics Fc epsilon RI-mediated activation of PLC-gamma 1 in RBL cells after permeabilization with Staphylococcus aureus alpha-toxin. Orthovanadate treatment of permeabilized cells induced: 1) a large increase in phosphoinositide hydrolysis in endogenously labeled cells; 2) an increase in PLC activity associated with the particulate fraction; and 3) an increase in immunoreactivity of PLC-gamma 1 in Western blots of the particulate fraction. In addition, incubation of RBL cells with either oligomeric IgE or orthovanadate results in the translocation of PLC-gamma 2 from the cytosol to the particulate fraction. All of the above effects were qualitatively similar to those seen after Fc epsilon RI aggregation. These data suggest that translocation and activation of PLC in mast cells are controlled by tyrosine phosphorylation of either the enzyme itself or some regulatory component. The equilibrium can be shifted to the phosphorylated state during either receptor-mediated activation of a tyrosine kinase or by blockade of dephosphorylation.

Animals↗

PubMed1993

Empiric long-term amiodarone prophylaxis following myocardial infarction. A meta-analysis.

BACKGROUND: The prophylactic administration of amiodarone following acute myocardial infarction has been investigated in several small trials. This study combined the results of these small trials in a meta-analysis to determine the effects of prophylactic low-dose amiodarone on mortality following acute myocardial infarction. METHODS: Four prospective, randomized, placebo-controlled trials, which investigated the prophylactic administration of low-dose amiodarone (200 to 400 mg/d) to patients after acute myocardial infarction, were selected from the current literature according to strict inclusion criteria. A total of 1140 patients, 566 in the amiodarone-treated group and 574 in the placebo-treated group, were included in the analysis. Sudden cardiac death, cardiac mortality, and total mortality were the end points of interest. In addition, the effect of impaired left ventricular function (ejection fraction, < 45%) on total mortality was assessed. Data were aggregated by using the Mantel-Haenszel method to obtain final summary statistics for these end points. RESULTS: Patients treated with low-dose amiodarone exhibited a lower incidence of sudden cardia death (3.1%) and total mortality (6.1%) when compared with patients treated with placebo (6.9% and 11.2%, respectively; both P < .01; and 95% confidence interval [CI], 0.011 to 0.065 and 0.013 to 0.082, respectively). There was no significant difference between the amiodarone- and placebo-treated groups with respect to cardiac mortality (2.6% vs 3.7%, respectively; P = .26; and 95% CI, -0.012 to 0.032). For patients with a left ventricular ejection fraction of less than 45%, total mortality was 5.5% in the amiodarone-treated group and 9.4% in the placebo-treated group (P = .30; CI, -0.023 to 0.101). CONCLUSIONS: Although further data from ongoing large, randomized trials are needed, this meta-analysis suggests that the prophylactic administration of low-dose amiodarone to patients following acute myocardial infarction reduces the incidence of both sudden cardiac death and total mortality. The benefits of low-dose amiodarone may be limited to patients with preserved left ventricular function.

Aged↗

PubMed2003

Role of COX-1 and -2 in prostanoid generation and modulation of angiotensin II responses.

The role of cyclooxygenase (COX)-1 and -2 in prostanoid formation and modulation of pressor responses to ANG II was investigated in the pulmonary and systemic vascular beds in the rat. In the present study, selective COX-1 and -2 inhibitors attenuated increases in pulmonary arterial pressure and decreases in systemic arterial pressure in response to arachidonic acid but did not alter responses to PGE1 or U-46619. The selective COX-1 and -2 inhibitors did not modify systemic pressor responses to injections or infusions of ANG II or pulmonary pressor responses to injections of the peptide. COX-2 inhibitors did not alter, whereas a COX-1 inhibitor depressed, arachidonic acid-induced platelet aggregation. These data provide evidence in support of the hypothesis that prostanoid synthesis occurs by way of the COX-1 and -2 pathways in the pulmonary and systemic vascular beds but that pressor responses to ANG II are not mediated or modulated by these pathways in the rat.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗

PubMed1985

Human serotonectin: a blood glycoprotein that binds serotonin and is associated with platelets and white blood cells.

A glycoprotein that circulates in blood, binds to the surface of platelets, and also binds serotonin with high avidity and specificity, has previously been found in rats. This glycoprotein has been called serotonectin. We now report the purification and characterization of a similar circulating glycoprotein in human blood that we propose be called human serotonectin, to distinguish it from the rat protein. Human serotonectin binds serotonin with high affinity (Kd1 = 36 nM; Kd2 = 1.1 microM). Monospecific antisera were raised in rabbits to purified human serotonectin. These antibodies were used to locate human serotonectin immunocytochemically, for quantitative estimation of the glycoprotein, and for rapid preparation of material purified by affinity chromatography. Evidence was obtained that indicated that human serotonectin circulates in plasma and also binds to the surfaces of white blood cells and platelets but not to red blood cells. In bone marrow it is found on megakaryocytes and on developing white cells of the eosinophil line. The protein can be completely removed by washing with isotonic sucrose or salt solutions from the surfaces of white cells but similar treatment only partially (63% sucrose wash/73% salt wash) removes human serotonectin from platelets. Antibodies to human serotonectin antagonize the uptake of serotonin by platelets but do not inhibit platelet aggregation. These data show that humans, like rats, have a circulating serotonin-binding glycoprotein that is also present as a peripheral membrane protein on platelets. The human also differs from the rat serotonectin in binding to white cells. The material may function in platelet serotonin uptake in both humans and rats; however, its function, if any, with respect to white cells is obscure.

Antibodies↗

PubMed1999

Randomised controlled trial of effect of feedback on general practitioners' prescribing in Australia.

OBJECTIVE: To evaluate the effect on general practitioners' prescribing of feedback on their levels of prescribing. DESIGN: Randomised controlled trial. SETTING: General practice in rural Australia. PARTICIPANTS: 2440 full time recognised general practitioners practising in non-urban areas. INTERVENTION: Two sets of graphical displays (6 months apart) of their prescribing rates for 2 years, relative to those of their peers, were posted to participants. Data were provided for five main drug groups and were accompanied by educational newsletters. The control group received no information on their prescribing. MAIN OUTCOME MEASURES: Prescribing rates in the intervention and control groups for the five main drug groups, total prescribing and potential substitute prescribing and ordering before and after the interventions. RESULTS: The intervention and control groups had similar baseline characteristics (age, sex, patient mix, practices). Median prescribing rates for the two groups were almost identical before and after the interventions. Any changes in prescribing observed in the intervention group were also seen in the control group. There was no evidence that feedback reduced the variability in prescribing nor did it differentially affect the very high or very low prescribers. CONCLUSIONS: The form of feedback evaluated here-mailed, unsolicited, centralised, government sponsored, and based on aggregate data-had no impact on the prescribing levels of general practitioners.

Adult↗

PubMed2002

Rottlerin inhibits tonicity-dependent expression and action of TonEBP in a PKCdelta-independent fashion.

Novel protein kinase C (PKC) isoforms PKCdelta and PKCepsilon have recently been implicated in signaling by hypertonic stress. We investigated the role of the putative PKCdelta inhibitor rottlerin on tonicity-dependent gene regulation. In the renal medullary mIMCD3 cell line, rottlerin blocked tonicity-dependent transcription of a tonicity enhancer (TonE)-driven luciferase reporter gene, as well as tonicity-dependent transcription of the physiological tonicity effector gene aldose reductase, but not urea-dependent transcription. Consistent with these data, rottlerin inhibited tonicity-dependent expression of TonE binding protein (TonEBP) at the mRNA and protein levels. Another inhibitor of both novel and conventional PKC isoforms, GF-109203X, suppressed TonEBP-dependent transcription but failed to influence tonicity-inducible TonEBP expression. Global PKC downregulation with protracted phorbol ester treatment, however, failed to influence tonicity-dependent signaling, arguing against a PKCdelta-dependent mechanism of rottlerin action in this model. In addition, hypertonic stress failed to induce phosphorylation of PKCdelta. Furthermore, in a PC-12 cell model with a comparable degree of tonicity-dependent transcription, constitutive overexpression of dominant negative-acting PKCdelta or PKCepsilon effectively decreased tonicity signaling to extracellular signal-regulated kinase activation, as expected, but failed to influence TonE-dependent transcription. TonE-dependent transcription, however, remained rottlerin sensitive in this PC-12 cell model. In the aggregate, these data indicate that rottlerin dramatically inhibits tonicity-dependent TonEBP expression and TonE-dependent transcription but, despite its reputed mode of action, does so through a PKCdelta-independent pathway.

Acetophenones↗

PubMed1992

Seasonality of births in nineteenth-century urban Tasmania.

The monthly distribution of births for Hobart Town, Van Diemen's Land, during the period 1839-1859 is examined. Prior research on two rural registration districts in nineteenth-century Tasmania revealed patterns of birth seasonality. The pattern was responsive to both the distinctive seasonal rhythm of regional economic activities and the birth interval and differed from the pattern for all of Tasmania in the twentieth century. Here, I argue that the aggregate monthly pattern of births in a mid-nineteenth-century urban registration district was, by contrast, not seasonal. Some seasonality was found among farmers, seamen, and dealers in foodstuffs but not in other industry groups. Class differences were not apparent. The research establishes that the seasonal distribution of mid-nineteenth-century urban births corresponds neither to nineteenth-century rural patterns nor to the patterns evident in the twentieth century.

Birth Rate↗

PubMed2004

Rotational diffusivity of fractal clusters.

The rotational diffusion behavior of fractal clusters generated through an off-lattice cluster-cluster aggregation algorithm in both diffusion-limited cluster aggregation and reaction-limited cluster aggregation conditions is investigated. The extended Kirkwood-Riseman theory (Garcia de la Torre et al., Macromolecules, 1987) is used to estimate the cluster rotational diffusion tensor. The three eigenvalues of this tensor, which correspond to the three main rotational diffusivity values of the cluster, have been computed for each generated cluster. Once the eigenvalues have been sorted in ascending order, each of them has been averaged over several thousands of clusters. It is found that one of the three main average rotational diffusivities is substantially larger than the other two, indicating significant anisotropy of fractal clusters. Moreover, a rotational hydrodynamic radius Rh,r has been determined on the basis of the mean value of the three average rotational diffusivities, which is about 25% larger than the mean translational hydrodynamic radius Rh calculated through the same Kirkwood-Riseman theory. Finally, the obtained Rh,r values have been applied to interpret dynamic light scattering data from aggregating colloidal systems and to investigate the reliability of the assumption, Rh = Rh,r, typically made in the literature.

Journal Article↗

PubMed2005

Day care versus in-patient surgery for age-related cataract.

BACKGROUND: Age-related cataract accounts for more than 40% of cases of blindness in the world with the majority of people who are blind from cataract found in the developing world. With the increased number of people with cataract there is an urgent need for cataract surgery to be made available as a day care procedure. OBJECTIVES: To provide reliable evidence regarding the safety, feasibility, effectiveness and cost-effectiveness of cataract extraction performed as day care versus in-patient procedure. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials - CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) on The Cochrane Library (Issue 3 2004), MEDLINE (1966 to July 2004), EMBASE (1980 to August 2004) and LILACS (July 2004). SELECTION CRITERIA: This review includes randomised controlled trials comparing day care and in-patient surgery for age-related cataract. The primary outcome was the achievement of a satisfactory visual acuity six weeks after the operation. DATA COLLECTION AND ANALYSIS: Although two trials are included in the review, adequate data were available for only one trial and therefore pooling of data from studies was not attempted. A descriptive summary is presented. MAIN RESULTS: Two trials, involving a total of 1284 people, are included in this review. One trial reported statistically significant differences in early postoperative complication rates in the day care group, with an increased risk of increased intraocular pressure, which had no clinical relevance to visual outcomes four months postoperatively. The mean change in visual acuity (Snellen lines) of the operated eye four months postoperatively was 4.1 (standard deviation (SD) 2.3) for the day care group and 4.1 (SD 2.2) for the in-patient group and not statistically significant. The four-month postoperative mean change in quality of life score measured using the VF14 showed minimal differences between the two groups. Costs were 20% more for the in-patient group and this was attributed to higher costs for overnight stay. One study only reported hotel costs for the non-hospitalised participants making aggregation of data on costs impossible. AUTHORS' CONCLUSIONS: This review provides some evidence that there is a cost saving but no significant difference in outcome or risk of postoperative complications between day care and in-patient cataract surgery. This is based on one detailed and methodologically sound trial conducted in the developed world. The success, safety and cost-effectiveness of cataract surgery as a day care procedure appear to be acceptable but additional well-designed trials are required to confirm these perceptions.

Ambulatory Surgical Procedures↗