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PubMed2006

Incidence of four-generation family lineages: is timing of fertility or mortality a better explanation?

OBJECTIVES: This article estimates the percentage of lineages that include four or more generations for a sample of the U.S. population and explores how social status and race are related to lineage depth. METHODS: We assembled data from Waves 1 and 2 of the National Survey of Families and Households in order to estimate the proportion of adults in four or more generations for the Wave 2 sample (1992-1994). When necessary, we used various decision rules to overcome an absence of information about specific generations. We examine relationships between lineage depth and sociodemographic variables by using logistic regressions. RESULTS: The data show that 32% of the respondents were in lineages comprising four or more generations. Blacks and individuals of lower social class were more likely to be in four-generation lineages, especially shorter-gapped lineages. Whites and individuals of higher social class were not more likely to be in longer-gapped, four-generation lineages. DISCUSSION: The majority of the adult population in the early 1990s was in three-generation lineages. The verdict is still out on whether population aging results in the wholesale verticalization of lineages. Social differentials in four-generation lineages in the early 1990s were mainly due to differences in the timing of fertility, rather than mortality.

Adult↗

PubMed1979

Values and self-esteem in three generations of men and women.

Similarities and differences in values within families across three generations were examined. The relationship between values and self-esteem was also investigated. Sixty inter-generational triads (30M;30F) rated 14 values on a semantic-differential scale. The hypotheses of generational similarities in long-term, central (in Rokeach's terms, terminal) values and of generational differences in short term, specific (Rokeach's instrumental) values were generally supported. However, the hypothesized interactions of self-esteem and generation with values were only minimally supported by these data. There were no generational differences in the terminal values Equality, An Exciting Life, Freedom, and A Sense of Accomplishment. The oldest generation rated the instrumental values Ambition, Capability, Independence, and Intelligence higher than did the other generations. In addition, they rated the more work-oriented values of Education, Money, Success and Work highest. These findings are discussed as possible cohort rather than as age effects. Women rated Ambition, Education, and Intelligence more highly than men.

Adolescent↗

PubMedDate not supplied

Biological coagulation findings in third-generation oral contraceptives.

An increased risk of venous thrombosis has been demonstrated in women receiving oral contraceptives (OCs). This risk has been primarily associated with the oestrogen content, but recent studies showed that the progestogen may also play a role. A higher risk was found with the so-called third-generation (desogestrel, gestodene) as compared with the second-generation progestogens (levonorgestrel). The risk was approximately two-fold. These unexpected results have been the subject of many debates, and bias--such as selection bias--has been suggested. The existence of bias cannot be completely excluded, but the thrombotic risk seems however to be slightly higher with the third-generation progestins. Haemostatic changes have been observed during OC intake. Both coagulation and fibrinolytic activity are increased: the beneficial profibrinolytic effect may counterbalance the deleterious procoagulant effect. This may explain that the absolute risk of venous thromboembolism is low during OC treatments. Some women who have pre-existing haemostatic abnormalities such as deficiency in antithrombin or activated protein C resistance with factor V Leiden, may be at a higher risk. The biological plausibility of the increased risk related to the third-generation progestogens has been explored. Theoretically, this could be due to an increased coagulation or to a lack of increased fibrinolysis as compared with second-generation progestogens. The only difference presently reported with third-generation OCs is a decreased sensitivity to activated protein C, possibly resulting in a hypercoagulability of greater magnitude. The selection bias suggested in epidemiological studies may also exist for the latter study, as women taking third- or second-generation OCs were not randomized. The possible increased risk related to third-generation OCs should not change the known general contra-indications. Practical guidelines are proposed for women with personal or family history of venous thromboembolism, and for those with a congenital cause of thrombophilia.

Contraceptives, Oral↗

PubMed2005

Transformation of expression intensities across generations of Affymetrix microarrays using sequence matching and regression modeling.

The utility of previously generated microarray data is severely limited owing to small study size, leading to under-powered analysis, and failure of replication. Multiplicity of platforms and various sources of systematic noise limit the ability to compile existing data from similar studies. We present a model for transformation of data across different generations of Affymetrix arrays, developed using previously published datasets describing technical replicates performed with two generations of arrays. The transformation is based upon a probe set-specific regression model, generated from replicate measurements across platforms, performed using correlation coefficients. The model, when applied to the expression intensities of 5069 shared, sequence-matched probe sets in three different generations of Affymetrix Human oligonucleotide arrays, showed significant improvement in inter generation correlations between sample-wide means and individual probe set pairs. The approach was further validated by an observed reduction in Euclidean distance between signal intensities across generations for the predicted values. Finally, application of the model to independent, but related datasets resulted in improved clustering of samples based upon their biological, as opposed to technical, attributes. Our results suggest that this transformation method is a valuable tool for integrating microarray datasets from different generations of arrays.

Algorithms↗

PubMed2002

Comparison of the 1st, 2nd and 3rd generation Lawrence Livermore National Laboratory Torso phantoms.

The Lawrence Livermore National Laboratory (LLNL) Torso phantom, which is the de facto standard for lung counter calibration for low energy photon emitters, has undergone a number of revisions since its development. The first generation used real human bone: the second generation used synthetic bone and had a major design change; the third generation had more subtle material and mould changes. This work has compared a first generation, two second generation, and two third generation LLNL phantoms to see if there are any differences between the phantoms. The comparison of five LLNL phantoms using the same counting regions has shown that the second and third generation phantoms are essentially equivalent at low photon energies, but the first generation phantom shows an increased counting efficiency at low photon energies due to a design flaw. It is also apparent that these phantoms have maintained their performance characteristics over an extended period of time.

Absorptiometry, Photon↗

PubMedDate not supplied

Determination of extra renal clearance and generation rate of beta2-microglobulin in hemodialysis patients using a kinetic model.

Beta-2-microglobulin (beta2-m) has been proposed as a marker of middle molecules to assess one aspect of the efficacy of dialysis. Until now, few data have been published about extra renal (metabolic) clearance and generation rates of beta2-microglobulin, which are necessary for calculation of total clearance and mass removal of beta2-m in hemodialysis patients. We have developed a simple method to derive extra renal clearance and generation rates of beta2-m by measuring the pre and post dialysis blood concentrations of beta2-m using kinetic modeling. Ten stable hemodialysis patients were included in this study. Pre and post dialysis concentrations of beta2-m were measured during dialysis with low flux dialyzers (F6 HPS) and after 10 days switching to high flux dialyzers (F60S or Superflux). With a validated two pool model, the generation rate of beta2-m can be determined if extra renal clearance is known. Assuming the generation rate of beta2-m to be constant in each patient, the computer reiterated the calculation of extra renal clearance until the calculated generation rate was equal for both the low flux and the high flux dialyzer. Extra renal clearance was found to be between 1.97 and 4.11 ml/min (average, 3.2 ml/min). Generation rate was found in a rather narrow range between 1.63 and 2.56 mg/kg per day (average, 2.09 mg/kg per day). There was no correlation between extra renal clearance and generation rates. With this simple method, extra renal clearance and generation rates of beta2-m can be determined using data by switching hemodialysis patients from impermeable to permeable membranes.

Age Factors↗

PubMed2004

Quantitative investigation of the vibration pattern of the substitute voice generator.

After a total excision of the larynx, mucosal tissue at the upper part of the esophagus can be used as a substitute voice generating element. The properties of the tissue dynamics are closely related to the substitute voice quality. The process of substitute voice is investigated by recording simultaneously the acoustic signal with a microphone and the vibrations of the voice generator with a digital high-speed camera. We propose an automatic image-processing technique which is applied to analyze the vibration pattern of the substitute voice generating element. First, an initialization step detects the voice generator within a high-speed sequence. Second, a combination of a threshold technique and an active contour algorithm tracks the tissue deformations of the substitute voice generator. The applicability of the algorithm is shown in three high-speed recordings. For the first time, tissue deformations of substitute voice generating elements are successfully tracked. The results of the image processing procedure are used to describe quantitatively the temporal properties of the substitute voice generator. Comparisons of the spectral components of tissue deformations and tracheoesophageal voice signals reveal the close relationship between the vibration pattern of the substitute voice generator and the quality of substitute voice.

Aged↗

PubMed2005

Generation of 8-hydroxydeoxyguanosine from DNA using rat liver homogenates.

In relation to carcinogenesis, aging and other pathologic conditions, urinary 8-hydroxydeoxyguanosine (8OHdG) is widely used as a marker for evaluating the effect of oxidative stress on DNA. Because no reports have described how 8OHdG is generated from DNA in vivo or by biological materials, and how it is excreted into urine, the authors investigated the generation of 8OHdG from DNA, using rat liver homogenate. Oxidatively damaged DNA samples containing different levels of 8OHdG were prepared using ultraviolet irradiation with three different concentrations of riboflavin. Following incubation of damaged DNA samples with rat liver homogenates, the generation of 8OHdG from the DNA was determined using high-performance liquid chromatography with electrochemical detection after ultrafiltration of the incubation mixtures. The generation of 8OHdG was also tested with an anti-8OHdG antibody. The quantity of 8OHdG generated from the DNA by rat liver homogenates was dependent on the 8OHdG levels in the DNA: almost all 8OHdG in the DNA was released as 8OHdG by rat liver homogenates. Generation of 8OHdG correlated with the degradation of DNA. Interestingly, the generated 8OHdG was stable in the presence of rat liver homogenates, whereas deoxyguanosine (dG) rapidly disappeared in the same conditions. Less than 1/10,000 of dG was converted to 8OHdG when dG was incubated with rat liver homogenate. Incubation of 8-hydroxyguanine with rat liver homogenates did not generate 8OHdG. These findings suggest that most of the 8OHdG in DNA is released as 8OHdG during DNA degradation and that, because of its stability, 8OHdG is excreted into urine, thus providing a convenient measure of oxidative damage to DNA.

8-Hydroxy-2'-Deoxyguanosine↗

PubMed1994

A flow cytometric method for measurement of hydrogen peroxide generation by pediatric polymorphonuclear leukocytes stimulated by Staphylococcus aureus and Escherichia coli.

The generation of hydrogen peroxide (H2O2), one of the reactive oxygen species, by polymorphonuclear leukocytes (PMN) stimulated by Staphylococcus aureus and Escherichia coli was studied in infants by cytofluorography. After heparinized whole blood was incubated with bacteria for 60 min, generated H2O2 was measured. The positive rate of H2O2 generation of PMN and mean fluorescent intensity of positive PMN stimulated by S. aureus and E. coli were significantly reduced in infants aged < 1 year and H2O2 generation increased with advancing age. In 10-15 year old children, the level of generated H2O2 reached adult levels. When sera from 1 year old children were added to separated PMN from healthy adults, H2O2 generation was reduced. In contrast, H2O2 generation by PMN from 1 year old children was increased by the addition of adult sera. These results suggest that the ability to generate H2O2 in response to S. aureus and E. coli is lower in infants and that such reduced activity may be related to the susceptibility of such infants to S. aureus and E. coli infections.

Adolescent↗

PubMed1996

Regulation of neutrophil superoxide generation by alpha-tocopherol in human peripheral and umbilical-cord blood.

OBJECTIVES: Alfa-tocopherol (VE) inhibits protein phosphorylation and affects protein kinase C (PKC)-dependent superoxide (O2) generation of phagocytic cells. Because umbilical-cord blood contains low concentrations of VE, we studied the effects of VE on stimulation-dependent O2 generation of neutrophils derived from the healthy human peripheral circulation (HPMNs) and the umbilical cord (UCBNs). METHODS: O2- generation and VE content were assayed by reduction of ferricytochrome c and by HPLC with an electrochemical detector, respectively. Neutrophil-specific annexin protein was identified by an immunological method. RESULTS: Both types of neutrophils generate significant amounts of PKC-dependent O2-generation, but weak PKC-independent O2-generation, except for opsonized zymosan-stimulated O2- generation in UCBNs. The VE content of UCBNs was similar to that of HPMNs although umbilical-cord blood contains a low concentration of VE. A neutrophil-specific annexin protein was also found in the UCBNs. CONCLUSION: UCBNs have a greater ability to incorporate VE than HPMNs do, but have similar general characteristics of stimulation-dependent O2-generation to those of HPMNs.

Annexin A1↗

PubMed2006

Generativity and successful parenting: an analysis of young adult outcomes.

Generativity scores were assessed in parents and correlated with offspring outcomes. The offspring were participants in a longitudinal study spanning their first and senior years of college. Generativity of parents was positively related to offspring agreeableness and conscientiousness. Parental generativity was also related to offspring scores on future time orientation and positive affect. In addition, generative parents seemed to model their political interests to offspring, and that modeling was related to children's higher scores on generativity and greater interest in politics. Parental generativity was also related to offspring religiosity. Most of these relationships remained significant after controlling for offspring scores on generativity. Generativity of parents appears to be related to successful offspring outcomes.

Adult↗

PubMed1989

Generation of histamine-releasing activity from serum albumin by medium derived from stimulated neutrophils of rat.

1. Medium conditioned by rat neutrophils stimulated by N-formyl-methionyl-leucyl-phenylalanine (FMLP) has been found to generate mast cell histamine-releasing activity (HRA) when incubated with bovine serum albumin (BSA). 2. Histamine release increased as the concentration of BSA used to generate HRA was increased from 0.25 to 10 mg ml-1, as the concentration of neurotrophil conditioned medium was increased and as the concentration of FMLP used to stimulate the neutrophils was increased. Histamine release was non-cytotoxic as it was inhibited by energy deprivation or by removal of calcium and it was accompanied by degranulation. 3. HRA was detectable after 30 min of incubation with BSA and its generation continued to increase over the 18 h of our measurements. 4. Generation of HRA was dependent upon the presence of medium from stimulated neutrophils and on the presence of BSA, although plasma could substitute for BSA. Likewise, HRA could be generated from gamma-globulin although to a lesser extent than with albumin. 5. Generation was optimum at acid pH and was inhibited by prior boiling of the neutrophil conditioned medium or by the addition of pepstatin. 6. It is suggested that an enzyme(s) released from the neutrophil during stimulation acts on an albumin-like substrate to generate HRA. It is proposed that HRA is peptide in nature and may be generated during an inflammatory response.

Animals↗

PubMed1995

Enhancing and inhibitory effects of nitric oxide on superoxide anion generation in human polymorphonuclear leukocytes.

1. The effects of sodium nitroprusside (SNP, a nitric oxide donor) and authentic nitric oxide (NO) on superoxide anion (O2-) generation were investigated in human polymorphonuclear leukocytes (PMNs). 2. Neither SNP (10 nM to 10 microM) nor NO (40 nM to 40 microM) alone induced O2- generation or change of intracellular Ca2+ concentration ([Ca2+]i) in human PMNs. 3. Pretreatment with SNP or NO at the concentrations used (SNP, 10 nM to 10 microM: NO, 40 nM to 40 microM) showed a biphasic concentration-dependent effect on O2- generation induced by f-methionyl-leucyl-phenylalanine (FMLP). Low concentrations of SNP (10 nM to 100 nM) and NO (400 nM) did not affect either basal cyclic GMP levels or cyclic GMP levels stimulated by FMLP, but enhanced FMLP-induced O2- generation and [Ca2+]i elevation. On the other hand, high concentrations of SNP (10 microM) and NO (40 microM) alone elevated cyclic GMP levels and inhibited FMLP-induced O2- generation and [Ca2+]i elevation. 4. 8-Bromo-cyclic GMP (8-Br-cyclic GMP) at concentrations ranging from 1 microM to 1 mM did not induce O2- generation on its own and had little effect on FMLP-induced O2- generation and [Ca2+]i elevation. 5. Addition of a high concentration of NO (40 microM) decreased authentic O2- formation by pyrogallol in a cell-free system, but a low concentration of NO (400 nM) had no effect on this. On the other hand, addition of SNP in the concentration-ranges used had no effect on authentic O2- formation by pyrogallol. 6. In this study, we have shown that SNP and NO have dual effects (enhancement and inhibition) on 02- generation induced by FMLP in human peripheral PMNs. The results suggest that the enhancement observed with SNP and NO at low concentrations is not mediated by activation of the guanylate cyclase-cyclic GMP pathway. The suppressive effect of SNP and NO at higher concentrations is mediated by the NO-induced O2--scavenging effect and activation of the guanylate cyclase-cyclic GMP pathway.

Calcium↗

PubMed2006

Thrombin generation in vascular tissue.

BACKGROUND: Classically, it is thought that the vast majority of thrombin is generated on the surface of platelets, however, thrombotic events occur in patients despite treatment with potent antiplatelet agents. METHODS AND RESULTS: In freshly harvested left internal mammary artery (IMA) sections, addition of CaCl2 and platelet-poor plasma (PPP) were sufficient to stimulate a profound burst of thrombin and this effect was inhibited by antitissue factor antibodies. Ultracentrifugation of PPP to remove platelet microparticles had no effect on thrombin generation. Both the extrinsic and factor VIII-dependent pathways were necessary for IMA-supported thrombin generation as PPP derived from individuals deficient in factors V, VII, VIII or X did not support thrombin production. Small amounts of thrombin were generated utilizing factor IX (FIX)-deficient plasma, however, thrombin was not generated by aorta from FIX-deficient mice when FIX-deficient plasma was used. The addition of non-lipidated tissue factor (0.6 pM) and CaCl2 to actively proliferating cultured human aortic smooth muscle cells (SMC) resulted in a pronounced burst of thrombin generation occurring between 3 and 15 min after treatment. In the absence of tissue factor, thrombin was generated but at a slower rate and with a peak value 26% of that observed in the presence of tissue factor. CONCLUSION: Significant thrombin generation can occur on vascular tissue in the absence of platelets or platelet microparticles and on the surface of non-apoptotic SMC.

Aorta↗

PubMed2006

P2Y12 receptor-mediated potentiation of thrombin-induced thromboxane A2 generation in platelets occurs through regulation of Erk1/2 activation.

BACKGROUND: Thromboxane A2 (TXA2) is a positive feedback lipid mediator that is generated upon stimulation of platelets with various agonists. Aspirin works as an antithrombotic drug by blocking the generation of TXA2. The aim of this study was to evaluate the role of the purinergic P2Y receptors in thrombin-induced TXA2 generation. RESULTS: PAR1-activating peptide (SFLLRN), PAR4-activating peptide (AYPGKF), and thrombin, induced the activation of cytosolic phospholipase A2 (cPLA2), release of arachidonic acid (AA) from membrane-bound phospholipids, and subsequent TXA2 generation in human platelets. The actions of these agonists were significantly inhibited in the presence of the P2Y12 receptor antagonist, AR-C69931MX, but not the P2Y1 receptor antagonist, MRS2179. In addition, AYPGKF- and thrombin-induced TXA2 generation was significantly reduced in platelets from mice dosed with clopidogrel, confirming the results obtained with the human platelets. Also, Pearl mouse platelets that lack releasable nucleotides generated significantly less TXA2 when compared with the wild-type littermates in response to PAR stimulation. Inhibition of extracellular signal-regulated protein kinase 1/2 (Erk 1/2) activation using U0126, an inhibitor of MAP kinase kinase (MEK), suppressed PAR-mediated cPLA2 phosphorylation and TXA2 generation. Further, platelets that were pretreated with AR-C69931MX, as well as Pearl mouse platelets, displayed the reduced levels of Erk1/2 phosphorylation upon stimulation with the PAR agonists. CONCLUSIONS: Based on these findings, we conclude that thrombin-induced Erk1/2 activation is essential for PAR-mediated TXA2 generation, which is potentiated by the P2Y12 receptor-mediated signaling pathway but not the P2Y1 receptor-mediated signaling pathway. Finally, using selective inhibitors of Src kinases, we show that PAR-mediated Src activation precedes Erk1/2 activation.

Adenosine Monophosphate↗

PubMed1996

The impact of pulse generator longevity on the long-term costs of cardiac pacing.

The long-term costs of cardiac pacing include the device costs, the procedural costs, the follow-up costs, and the replacement costs. At present, there is significant variability in the efficiencies of the integrated circuits and the total battery capacity among different pulse generators that will influence replacement rates over time. Accordingly, we compared the influence of pulse generator longevity on the long-term costs of pacing. The longevity of pulse generators was calculated based on the electrical characteristics of the device and the percentage of time the patient is paced. Replacement rates of pulse generators were estimated for our patient population over a 20-year period, based on patient survival and pulse generator longevity. The costs of pacing over this 20-year follow-up period were then calculated. The longevity of DDDR devices presently implanted in the United States ranges from 8-14 years, assuming that patients are paced 50% of the time. Replacement rates in this population over a 20-year follow-up period were calculated to range from 0.34-0.66, and the total costs of pacing would range from $11,898-14,900 per patient. The longevity of SSIR devices ranges from 7-20 years, assuming that patients are paced 50% of the time. Replacement rates were calculated over the 20-year follow-up period to range from 0.20-0.84, and the total costs of VVIR pacing would range from $8,331-13,286. Based on the proportion of pulse generator models implanted in patients in the United States, the maximum cost differential to the health care system is approximately $424 million/year comparing the devices with the shortest and greatest longevities. Thus, pulse generator longevity may significantly influence the long-term costs of pacing. Patient survival and pulse generator system longevity should be considered when selecting the appropriate pacing system for the individual patient.

Actuarial Analysis↗

PubMed1997

Is smoking in pregnancy interrelated between generations?

In order to compare pregnancy smoking habits in two generations, data on first generation deliveries in 1964-67 were obtained from prospective questionnaires. By record linkage with the Swedish Medical Birth Registry, data on daughters giving second generation births (n = 1659) were obtained, including prospective smoking information. The catchment area was that of Helsingborg County Hospital (population 145,000). Second generation births until December 31, 1993 were identified in all of Sweden. The odds ratio of maternal smoking in the first generation for pregnancy smoking among the daughters was significantly increased and approximately doubled. Adjustment for confounders was made using the Mantel-Haenszel method. Similar odds ratios remained after stratification either for a social environment index of the first generation or the educational level of the second generation. Thus, our data suggest a biological association between pregnancy smoking habits over generations. Research on causative mechanisms could help design more efficient intervention programs. In a separate analysis of two parturient cohorts in Helsingborg 30 y apart, we found that the prevalence of maternal smoking had decreased comparatively more among younger than older women.

Adolescent↗

PubMed1995

Role of the ferret perigeniculate nucleus in the generation of synchronized oscillations in vitro.

1. The cellular mechanisms by which neurons of the ferret perigeniculate nucleus (PGN) participate in the generation of spindle waves and slowed absence seizure-like oscillations were investigated with intracellular and extracellular recording techniques in geniculate slices maintained in vitro. 2. During spindle wave generation, PGN neurons generated repetitive (2-9 Hz) high frequency (up to 500 Hz) burst discharges mediated by the activation of a low threshold Ca2+ spike by the arrival of barrages of excitatory postsynaptic potentials (EPSPs). In most PGN cells at resting membrane potentials (-60 to -70 mV) spindle waves were associated with a progressive hyperpolarization that persisted as a prolonged after-hyperpolarization. 3. The EPSPs occurring in PGN cells were highly synchronized with burst firing in the neighbouring portion of the dorsal lateral geniculate nucleus (LGNd) and were intermixed with short duration inhibitory postsynaptic potentials (IPSPs). After block of GABAergic receptors, the EPSPs occurring during the generation of spindle waves reversed polarity at around 0 mV. In addition, these EPSPs were completely blocked with the bath application of the non-NMDA receptor antagonist 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), as was spindle wave generation in both the PGN and LGNd. 4. Slowing the intraspindle frequency to 2-4 Hz with pharmacological block of GABAA receptors resulted in a marked increase in the intensity of burst firing by PGN cells such that the number of action potentials per burst increased from a maximum of thirteen to a maximum of sixty. Block of GABAA receptors also resulted in a marked increase in the amplitude and duration of the EPSP barrages arriving from the relay laminae during generation of the slowed oscillation. 5. These findings indicate that spindle waves are generated in the ferret LGNd in vitro through an interaction between the GABAergic neurons of the PGN and relay neurons, such that burst firing in relay neurons activates a barrage of EPSPs and a subsequent low threshold Ca2+ spike in PGN cells. This activation of PGN neurons inhibits a substantial number of relay cells, a few of which rebound burst after this IPSP, thus starting the cycle again. Block of GABAA receptors results in a marked enhancement of activity in PGN cells through increased excitation from relay cells and disinhibition from neighbouring PGN cells. This increased activity in PGN neurons results in a markedly enhanced activation of GABAB receptors in relay neurons and the subsequent generation of paroxysmal activity that is similar to that associated with absence seizures.

Animals↗