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PubMed1995

The influence of allo-class II MHC-specific Th2 cells on the generation of CD4 and CD8 cytotoxic T cells to associated class I and class II MHC alloantigen.

There is considerable interest in whether CD4 T cell function can affect the outcome of allogeneic transplants. In mice tolerant to an isolated class II MHC disparity, the normal Th1 activity in vitro associated with graft rejection is switched to Th2 in tolerant animals. Because clinical transplants involve multiple class I and II MHC disparities we tested how the switch to Th2 activity of tolerant mice would affect the generation of CD4 and CD8 cytotoxic T cells (CTL) against MHC alloantigens to which the mice were not tolerant. A.TH mice (KkIsDd) were rendered neonatally tolerant of A.TL (KkIkDd) and the generation of CD4 or CD8 CTL measured in a mixed lymphocyte reaction (MLR) against (A.TL x B6)F1 stimulators. Normal mice generated CD4 CTL against both A.TL and B6 (KbIbDb), but tolerant mice were unable to generate cytotoxicity against either A.TL or B6. However, tolerant cells were able to generate CD8 CTL against B6. IL-4 inhibited the generation of CD4, but not CD8, CTL by normal cells and anti-IL-4 antibody was shown to increase the generation of CD4 CTL against B6 in F1 stimulated cultures. Overall the results showed that a Th2 response could inhibit the generation of CD4 CTL against concomitant alloantigen in a process at least partially involving IL-4, but that, conversely, tolerant Th2 cells could help in the generation of CD8 CTL. The results suggest that with whole MHC disparities a simple change of CD4 T cells to Th2 would not be enough to procure graft acceptance.

Animals↗

PubMed2005

Understanding generations: political economy and culture in an ageing society.

Sociological understanding of generations can be enhanced by avoiding defining them rigidly as chronological cohorts but rather linking people's accounts of their generational experience with an historically informed political economy. It then becomes possible, for example, to understand the complexity of generational politics. This paper uses data on the 'War Generation' taken from the Exeter Politics of Old Age project to link an empirically based political economy of generational inequality with a cultural sociology of generations. The 'War Generation' recognizes itself and is referred to by others in terms of a common identity. It is also an historical generation; its values, attitudes and, above all, sense of national solidarity and mutual obligation were forged in the direct experience of war. But it is also divided by divergent economic interests in property and pension rights based on the historical experience of the life course by successive groups and this segmentation can be observed in political action. The political culture of the War Generation manifests both continuity and change. Understanding these dynamics requires listening to people constructing their worlds, understanding their full range of historical experiences, and analysing the conditions for their conflicts and their cohesion.

Aged↗

PubMed1994

Changes in brain MAO activity and glycogen levels upon chronic alcoholization of three successive generations of rats.

Changes in neurobiological parameters were examined from early life (10 days post-natal) until late adulthood (8 months post-natal) in three successive generations of alcoholized rats. The mean daily consumption of alcohol by the 2nd and 3rd generation rats (7.40 +/- 0.22 and 7.70 +/- 0.20 g ethanol/kg body weight, respectively) was significantly greater than that of the 1st generation alcoholized group (4.26 +/- 0.33 g/kg). Brain/body weight ratios of alcoholized rats, 10 days post-natal, were significantly greater than controls, with 1st generation alcoholized rats presenting significantly greater brain/body weight ratios than those of the 2nd or 3rd generation, which tended toward control weights and ratios. This difference between alcoholized rats and controls persisted, although to a lesser extent, at 8 months post-natal. Glycogen content in the brains of rats of all alcoholized generations was significantly lower than in controls at 10 days post-natal, with a reversal of this situation in later life for 2nd and 3rd generation rats, which presented significantly greater cerebral glycogen levels than control or 1st generation alcoholized rats (which had an equivalent cerebral glycogen content). In 10-day-old rat pups, monoamine oxidase (MAO) activity in brain tissues had a tendency (mostly non-significant) to be greater in alcoholized rats than in controls, with a reversal of this situation, ie a statistically significant decrease in MAO activity in the 2nd and 3rd alcoholized generations with respect to controls, in 8-month-old rats. MAO activity in adrenal glands of alcoholized rats was greater than in controls at 10 days post-natal, and this difference persisted at 8 months.

Alcoholism↗

PubMed2005

In high glucose protein kinase C-zeta activation is required for mesangial cell generation of reactive oxygen species.

BACKGROUND: We postulated that in mesangial cells exposed to high glucose, protein kinase C-zeta (PKC-zeta) is necessary for the generation of reactive oxygen species (ROS) by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and that the requirement of PKC-zeta for filamentous (F)-actin disassembly may involve ROS. To identify signaling mechanisms relevant to PKC-zeta activation and ROS generation, including phosphoinositide 3 kinase (PI3 kinase), we examined mesangial cell stimulation with platelet-derived growth factor (PDGF). METHODS: In primary rat mesangial cells cultured in 5.6 mmol/L or 30 mmol/L d-glucose, PKC-zeta expression was identified with immunoblotting and activity was analyzed in cell membrane immunoprecipitates and by confocal immunofluorescence imaging. ROS generation was measured by dichlorofluorescein fluorescence using confocal microscopy and was inhibited by transfection of antisense against NADPH subunits p22(phox) or p47(phox) or with Tempol. F-actin disassembly was observed by dual-channel confocal fluorescence imaging. PI3 kinase activity was detected by immunoblotting of phosphorylated Akt. RESULTS: In high glucose, generation of NADPH oxidase-dependent ROS was dependent on PKC-zeta. Conversely, sustained PKC-zeta activity was dependent on ROS generation, suggesting a positive feedback. PKC-zeta-dependent F-actin disassembly in high glucose required ROS generation. PDGF stimulated NADPH oxidase generation of ROS through a PKC-zeta mechanism that was independent of Akt phosphorylation and remained unchanged in high glucose. CONCLUSION: In high glucose, mesangial cell PKC-zeta is required for ROS generation from NADPH oxidase similar to PDGF stimulation of PKC-zeta-dependent ROS generation through a pathway independent of PI3 kinase. F-actin disassembly in high glucose also requires ROS. A positive feedback loop occurs between ROS and the activation of PKC-zeta in high glucose.

Actins↗

PubMed1995

Generation of neurons in the rat dentate gyrus and hippocampus: effects of prenatal and postnatal treatment with ethanol.

Neurons in the rat hippocampal formation (the dentate gyrus and the hippocampus) are born over a protracted period, from gestational day (G) 15 into adulthood. Dentate gyral neurons born prenatally are generated from the ventricular zone, whereas those born postnatally are derived from a secondary proliferative zone, the intrahilar zone. In contrast, hippocampal pyramidal neurons are generated only prenatally from the ventricular zone. In the neocortex, ethanol depresses the proliferation of cells in the ventricular zone and stimulates the proliferation of cells in the secondary proliferative zone. The present study tests the hypotheses that prenatal treatment with ethanol has a different effect on the generation of dentate gyral neurons than does postnatal ethanol treatment, and that these differences are determined by the timing of the ethanol exposure relative to the period and site of neuronal generation. Rats were treated with ethanol between G6 and G21 or between postnatal day (P) 4 and P12. They were given an injection of [3H]thymidine on G15, G18, G21, P6, P9, or P12. Rats were killed on P30-P35. The tissue was processed by standard autoradiographic methods and assessed using rigorous stereological procedures. The total number of neurons and the density of radiolabelled neurons in both the dentate gyrus and the CA1 region of the hippocampus were determined. Prenatal ethanol treatment decreased the total number of neurons in the CA1 segment of the hippocampus and had little impact on neuronal number in the dentate gyrus. Likewise, the number of hippocampal and dentate gyral neurons generated daily was significantly lower in ethanol-treated rats than in controls. Postnatal treatment to ethanol, however, significantly increased the total number of dentate gyral neurons and the density of neurons generated postnatally. These postnatal changes depended on the blood ethanol concentration (BEC). At moderate BECs, the total number of neurons in the dentate gyrus and the number of neurons generated was increased. At high BECs, however, neuronal number and neuronal generation were decreased. Postnatal ethanol treatment had no effect on the number of (total or radiolabeled) CA1 neurons. Thus, pre- and postnatal exposure to ethanol have opposite effects both on the number of neurons in the dentate gyrus and on the generation of neurons. These paradoxical effects likely result from three causes: the differential effects of ethanol on the two proliferative zones, the critical period of neuronal development, and the potentially opposite effects of moderate and high BEC.

Animals↗

PubMed2005

Effects of an ozone-generating air purifier on indoor secondary particles in three residential dwellings.

UNLABELLED: The use of indoor ozone generators as air purifiers has steadily increased over the past decade. Many ozone generators are marketed to consumers for their ability to eliminate odors and microbial agents and to improve health. In addition to the harmful effects of ozone, recent studies have shown that heterogeneous and homogeneous reactions between ozone and some unsaturated hydrocarbons can be an important source of indoor secondary pollutants, including free radicals, carbonyls, carboxylic acids, and fine particles. Experiments were conducted in one apartment and two detached single-family dwellings in Austin, TX, to assess the effects of an ozone generator on indoor secondary organic aerosol concentrations in actual residential settings. Ozone was generated using a commercial ozone generator marketed as an air purifier, and particle measurements were recorded before, during, and after the release of terpenes from a pine oil-based cleaning product. Particle number concentration, ozone concentration, and air exchange rate were measured during each experiment. Particle number and mass concentrations increased when both terpenes and ozone were present at elevated levels. Experimental results indicate that ozone generators in the presence of terpene sources facilitate the growth of indoor fine particles in residential indoor atmospheres. Human exposure to secondary organic particles can be reduced by minimizing the intentional release of ozone, particularly in the presence of terpene sources. PRACTICAL IMPLICATIONS: Past studies have shown that ozone-initiated indoor chemistry can lead to elevated concentrations of fine particulate matter, but have generally been completed in controlled laboratory environments and office buildings. We explored the effects of an explicit ozone generator marketed as an air purifier on the formation of secondary organic aerosol mass in actual residential indoor settings. Results indicate significant increases in number and mass concentrations for particles <0.7 microns in diameter, particularly when an ozone generator is used in the presence of a terpene source such as a pine oil-based cleaner. These results add evidence to the potentially harmful effects of ozone generation in residential environments.

Aerosols↗

PubMed1998

Reduction of diagnostic window by new fourth-generation human immunodeficiency virus screening assays.

In order to reduce the diagnostic window between the time of human immunodeficiency virus (HIV) infection and laboratory diagnosis, new screening enzyme-linked immunosorbent assays (ELISAs) which permit the simultaneous detection of HIV antigen and antibody have been developed. Two fourth-generation assays, HIV DUO (Biomérieux) and HIV Combi (Boehringer Mannheim), for the combined detection of HIV antigen and antibody, were compared with a third-generation assay (HIV-1/HIV-2 3rd Generation Plus enzyme immunoassay [EIA]; Abbott) and a p24 antigen test (HIV-1 Ag monoclonal; Abbott). A total of 17 seroconversion panels, 15 cell culture supernatants infected with different HIV type 1 (HIV-1) subtypes, and 255 potentially cross-reactive serum samples were tested. Ten seroconversions were detected an average of 8.1 days earlier with HIV DUO and 7.5 days earlier with HIV Combi than with the third-generation ELISA. Overall, in the 17 seroconversion panels tested, HIV DUO detected HIV-1 infection an average of 4.8 days and HIV Combi detected infection an average of 4.4 days earlier than HIV-1/HIV-2 3rd Generation Plus EIA. HIV antigen was detected with HIV DUO and HIV Combi in all of the 15 cell culture supernatants infected with different HIV-1 subtypes, including subtype O. With fourth-generation assays, considerably fewer false-positive results (n = 4 to 6) were obtained, in comparison with the third-generation EIA (n = 18). Fourth-generation assays permit an earlier diagnosis of HIV infection than third-generation antibody screening assays through the detection of p24 antigen, which may be present in serum samples from individuals with recent HIV infection prior to seroconversion.

AIDS Serodiagnosis↗

PubMed2003

Exogenous nitric oxide generates ROS and induces cardioprotection: involvement of PKG, mitochondrial KATP channels, and ERK.

We examined whether cGMP-dependent protein kinase (PKG) and mitochondrial ATP-sensitive potassium (K(ATP)) channels are involved in S-nitroso-N-acetyl penicillamine (SNAP)-induced reactive oxygen species (ROS) generation. SNAP significantly increased ROS generation in cardiomyocytes. This increase was suppressed by both 5-hydroxydecanoate (5-HD) and glibenclamide. Direct opening of mitochondrial K(ATP) channels with diazoxide led to ROS generation. The increased ROS generation was reversed by N-(2-mercaptopropionyl)glycine (MPG), a scavenger of ROS. Myxothiazol partially suppressed the ROS generation. KT-5823, an inhibitor of PKG, prevented ROS generation, indicating that PKG is required for ROS generation. In addition, 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP), an activator of PKG, induced ROS generation. The effect of 8-BrcGMP was reversed by either 5-HD or MPG. YC-1, an activator of guanylyl cyclase, also increased ROS production, which was reversed by 5-HD. Neither LY-294002 nor wortmannin, the inhibitors of phosphatidylinositol 3-kinase (PI3-kinase), affected SNAP's action. In a whole heart study, SNAP significantly reduced infarct size. The anti-infarct effect of SNAP was abrogated by either MPG or 5-HD. This effect was also blocked by PD-98059, an ERK inhibitor, but not by LY-294002. A Western blotting study showed that SNAP significantly enhanced phosphorylation of ERK, which was reversed by MPG. These results suggest that SNAP-induced ROS generation is mediated by activation of PKG and mitochondrial K(ATP) channels and that opening of mitochondrial K(ATP) channels is the downstream event of PKG activation. ROS and mitochondrial K(ATP) channels participate in the anti-infarct effect of SNAP. Moreover, phosphorylation of ERK is the downstream signaling event of ROS and plays a role in the cardioprotection of SNAP.

Animals↗

PubMed2006

Cost-effectiveness of second-generation antipsychotics and perphenazine in a randomized trial of treatment for chronic schizophrenia.

BACKGROUND: Second-generation antipsychotics have largely replaced first-generation antipsychotics for the treatment of schizophrenia, but a large-scale cost/effectiveness analysis has not been attempted. METHOD: Patients with schizophrenia (N=1,493) were assigned to treatment with a first-generation antipsychotic (perphenazine) or one of four second-generation drugs (olanzapine, quetia-pine, risperidone, or ziprasidone) and followed for up to 18 months. Patients with tardive dyskinesia were prohibited from assignment to perphenazine. Patients could be reassigned at any time to another second-generation drug, including clozapine, but not to perphenazine. The cost analysis included medications plus health services use. Quality-adjusted life year (QALY) ratings were assessed on the basis of Positive and Negative Syndrome Scale (PANSS) subscale scores and side effects. An intention-to-treat analysis included all available observations, classified by initial drug assignment, and costs of reassignment of most patients to another second-generation drug. The analysis was repeated considering only treatment on initially assigned medications. RESULTS: Although QALY ratings, PANSS scores, and other quality of life measures indicated modest improvement over 18 months, there were no significant differences between perphenazine and any second-generation medication. Average total monthly health care costs were 300 dollars-600 dollars (20%-30%) lower for perphenazine than for second-generation antipsychotics because of lower drug cost. Differences in costs remained when maximally discounted drug prices were used for all patients and when only observations during treatment with the first medication were included. CONCLUSIONS: Treatment with perphenazine was less costly than treatment with second-generation antipsychotics with no significant differences in measures of effectiveness. However, the trial was limited by a high dropout rate, and longer-term neurological and metabolic side effects require further study.

Adolescent↗

PubMed1991

The cross-generation effect of neonatal macrosomia in rat pups of streptozotocin-induced diabetes.

To study the cross-generation effect of enhanced growth in macrosomic newborn rats, we induced mild hyperglycemia in 15 pregnant Sprague Dawley rats by intraperitoneal injection of streptozotocin, 35 mg/kg body weight, on the 5th d of gestation. As reported previously, we produced hyperinsulinemia and accelerated growth in the fetuses of hyperglycemic dams. We also showed that the macrosomic female pups (second generation) continued to have a higher growth rate through the first 12 wk of life. In this study, the second-generation female rats were mated with macrosomic second-generation males; they demonstrated glucose intolerance during late pregnancy and delivered pups (third generation) with higher birth weight and plasma insulin levels than the pups from control second-generation rats. When the macrosomic third-generation pups were raised under identical nutritional and environmental conditions as controls, the macrosomic rats showed accelerated growth and higher fat tissue weight during the first 12 wk of life. Furthermore, the macrosomia was associated with glucose intolerance and higher insulin to glucose ratios compared to controls. We also mated the offspring of second-generation streptozotocin-injected nonmacrosomic as well as the offspring of macrosomic pups of buffer-injected dams; none of the pups from these matings were significantly macrosomic. Therefore, we conclude that the perpetuation of obesity and possibly glucose intolerance across generations in this rat model is predominantly a result of abnormal intrauterine metabolic environment rather than genetic factor driven.

Animals↗

PubMed2001

The suppressive effect of dietary restriction and weight loss in the obese on the generation of reactive oxygen species by leukocytes, lipid peroxidation, and protein carbonylation.

Increased reactive oxygen species generation by the leukocytes of the obese may be responsible for increased oxidative injury to lipids and proteins and, hence, atherosclerosis. We have investigated whether reactive oxygen species generation by leukocytes and other indexes of oxidative damage in the body fall with short-term dietary restriction and weight loss. Nine nondiabetic obese subjects (body mass index, 32.5-64.4 kg/m(2)), not taking any antioxidants, were put on a 1000-Cal diet. Fasting blood samples were taken at 0, 1, 2, 3, and 4 weeks and at 12 weeks after the cessation of dietary restriction. Blood samples were also obtained at 1 and 2 h after administration of 75 g oral glucose at 0 and 4 weeks. Mononuclear cells (MNC) and polymorphonuclear leukocytes (PMN) were isolated, and reactive oxygen species generation was measured. Plasma concentrations of thiobarbituric acid-reactive species (TBARS), 13-hydroxyoctadecadienoic acid (13-HODE), 9-hydroxyoctadecadienoic acid (9-HODE), carbonylated proteins, o-tyrosine, and m-tyrosine as indexes of oxidative damage to lipids, proteins and amino acids, respectively, were measured. Antioxidant vitamins were measured as indexes of antioxidant reserves. Plasma tumor necrosis factor-alpha concentrations were also measured. Mean weight loss was 2.4 +/- 0.6 kg at week 1, 2.5 +/- 1.7 kg at week 2, 3.9 +/- 0.8 kg at week 3, and 4.5 +/- 2.8 kg at week 4 (P < 0.05). Reactive oxygen species generation by PMN fell from 236.4 +/- 95.8 to 150.9 +/- 69.0, 125.9 +/- 24.3, 96.0 +/- 39.9, and 103.1 +/- 35.7 mV at weeks 1, 2, 3, and 4, respectively (P < 0.001). It increased 3 months after the cessation of dietary restriction to 270.0 +/- 274.3 mV. Reactive oxygen species generation by MNC fell from 187.8 +/- 75.0 to 101.7 +/- 64.5, 86.9 +/- 42.8, 63.8 +/- 14.3, and 75.1 +/- 32.2 mV and increased thereafter to 302.0 +/- 175.5 mV at 1, 2, 3, 4, and 16 weeks, respectively (P < 0.005). Reactive oxygen species generation by PMN and MNC increased in response to glucose; the relative increase was greater at 4 weeks than that at week 0 due to a fall in the basal levels of reactive oxygen species generation. Consistent with the fall in reactive oxygen species generation, there was a reduction in plasma TBARS from 1.68 +/- 0.17 micromol/L at week 0 to 1.47 micromol/L at 4 weeks (P < 0.05). The 13-HODE to linoleic acid ratio fell from a baseline of 100% to 56.4 +/- 36.1% at 4 weeks (P < 0.05), and the 9-HODE to linoleic acid ratio fell from a baseline of 100% to 60.5 +/- 37.7% at 4 weeks (P < 0.05). Carbonylated proteins fell from 1.39 +/- 0.27 microgram/mg protein at week 0 to 1.17 +/- 0.12 microgram/mg protein at week 4 (P < 0.05); o-tyrosine fell from 0.42 +/- 0.03 mmol/mol phenylalanine at week 0 to 0.36 +/- 0.02 mmol/mol phenylalanine at 4 weeks (P < 0.005), and m-tyrosine fell from 0.45 +/- 0.04 mmol/mol phenylalanine at week 0 to 0.40 +/- 0.03 mmol/mol phenylalanine at 4 weeks (P < 0.05). The basal concentrations of TBARS, 9-HODE, 13-HODE, carbonylated proteins, o-tyrosine, and m-tyrosine in the obese were significantly greater than those in normal subjects. On the other hand, tumor necrosis factor-alpha concentrations did not change during this 4-week period, nor was there any change in antioxidant vitamins. This is the first demonstration of 1) an increase in reactive oxygen species-induced damage in lipids, proteins, and amino acids in the obese compared with normal subjects; and 2) a decrease in reactive oxygen species generation by leukocytes and oxidative damage to lipids, proteins, and amino acids after dietary restriction and weight loss in the obese over a short period.

Adult↗

PubMed2002

Poor reproducibility of IGF-I and IGF binding protein-3 generation test in children with short stature and normal coding region of the GH receptor gene.

The IGF-I generation test has been proposed to select patients with GH insensitivity. Studies have shown that children with idiopathic short stature and GH deficiency, who were expected to be sensitive to GH, presented absent IGF-I and IGF binding protein (IGFBP)-3 responses and/or discordant results at IGF-I and IGFBP-3 generation test for unknown reasons. To assess the reproducibility of the generation test, we studied a group of 12 prepubertal children with short stature and normal GH secretion in whom defects in coding region of GH receptor gene were ruled out. All patients underwent the test twice. Discordant responses between the first and second test were found in five and six patients for IGF-I and IGFBP-3, respectively. When the results of the generation tests were compared, one notices that IGF-I generation has more concordant positive results than IGFBP-3. In eight generation tests that showed discordant results between IGF-I and IGFBP-3, seven presented a positive IGF-I with a negative IGFBP-3 response. Taking both tests into account, all children presented a normal IGF-I generation. Our findings showed that IGF-I and IGFBP-3 generation test was not reproducible in children that should have responded to GH stimulation. We suggest that, when IGF-I and IGFBP-3 levels fail to respond in the generation test, another test should be performed to confirm GH insensitivity.

Adolescent↗

PubMedDate not supplied

Aspects related to productivity for four generations of a Lutzomyia longipalpis laboratory colony.

A closed colony of Lutzomyia longipalpis was established with specimens collected in the Raposa - Serra do Sol indian reservoir, one of the main foci of visceral leishmaniasis in the State of Roraima, Brazil. Biological observations were made on four generations of a L. longipalpis colony with emphasis on productivity. Aspects studied were the number of laid and retained eggs, and the number of adults (male and female) per generation. During the four generations the percentage of engorged females that laid eggs varied from 64.2% (third generation-F3) to 90.3% (second generation-F2). The mean number of eggs laid per female varied from 23.6 (F3) to 39. 9 (first generation-F1). The maximum number of eggs laid per female varied from 84 (F3) to 124 (F1). The mean number of retained eggs per female was 12.7 (parental generation-P and F1) to 22.1 (F2). The number of females exceeded the number of males in all generations. However, significant difference for male/female ratio was found only for F3. Fecundity rates were between 42.1 (F3) and 58.3 (F2). From a total of 439 blood-fed females, 355 females laid 12,257 eggs that yield 5,354 adults (2,525 males and 2,829 females) in four generations. F2 presented maximum productivity and fecundity rates.

Animals↗

PubMed1997

Divergent selection for heat loss in mice: II. Correlated responses in feed intake, body mass, body composition, and number born through fifteen generations.

Divergent selection for heat loss (kcal.kg-.75.d-1), measured in 9- to 11-wk-old male mice, was conducted for 15 generations. Selection for high (MH) and low (ML) heat loss and unselected control (MC) occurred in each of three replicates for a total of nine unique lines. Feed intake in males was measured during Generations 9 through 15. Body mass at commencement of mating in females and at time of measurement of heat loss in males was recorded. Body fat percentage at 12 wk for animals of Generations 6, 10, and 14 was predicted as a function of electrical conductivity and body mass. Litter size was recorded for all generations, and components of litter size were evaluated at Generation 11 in one replicate and Generation 12 in the other two replicates. Feed intake changed in the same direction as heat loss for the MH and ML selections; at Generation 15, the difference between MH and ML (P < .002) was 20.6% of the MC mean. Body mass did not change with selection for heat loss. Differences in body fat percentage were not significant in earlier generations, but at Generation 14, MH and ML were significantly (P < .01) different with MH mice having the lowest fat percentage; MC was intermediate. Selection had a significant (MH vs ML; P < .01) effect on litter size, causing an increase in MH and a decrease in ML. This difference was explained by a difference (P < .01) in ovulation rate. There was no asymmetry of response in feed intake, fatness, litter size, or number of ovulations.

Animals↗

PubMedDate not supplied

Serum thyrotropin determinations: comparison of second- and third-generation assays.

OBJECTIVE: To compare thyrotropin (thyroid-stimulating hormone or TSH) levels determined by second- and third-generation assays in sera extracted from blood samples withdrawn randomly from 34 subjects attending outpatient clinics. METHODS: Serum specimens were separated into two fractions and were frozen and stored at -20 degrees C for subsequent determination of TSH concentrations by second-and third-generation assays. The results were analyzed statistically. RESULTS: Of the 34 serum samples, 23 TSH levels were within normal ranges on both assays, whereas 9 samples showed subnormal TSH concentrations with both second- and third-generation assays. The other two samples revealed mildly increased TSH levels by the third-generation assay but high normal levels with the second-generation assay. Moreover, mean TSH values determined with second- and third-generation assays for all 34 serum samples were not significantly different (1.48 versus 1.66 mU/L; P>0.05). Finally, a highly significant correlation (r = 0.987) was also noted between the two assays on simple linear regression. CONCLUSION: Thus, serum TSH determinations by both the second- and third-generation assays are almost identical, and attempting to achieve greater sensitivity to detect lower levels by further modifications in third-, fourth-, and even later generation assays may be an expensive and fruitless endeavor because of the inability of these methods to discern the thyroid functional state any better than the second-generation assay.

Journal Article↗

PubMed1991

[Basal experiments of active oxygen generation in urinary polymorphonuclear leukocytes].

Polymorphonuclear leukocytes (PMNs) play an important role in host defense system. Upon interaction with soluble or particulate matter, PMNs generate active oxygen species (AO), which act on killing of bacteria. In urinary tract infection, urinary PMNs are assumed to have bactericidal activity in urine. Basal experiments were studied on the AO generation of urinary PMNs, monitored by mainly the luminol-dependent chemiluminescence. It was indicated that urinary PMNs, isolated from patients with urinary tract infection, generated AO in physiological medium. This activity of urinary PMNs was found to be significantly inhibited rather than that of PMNs in blood, and this suppression was suggested to be time-dependent. PMNs were affected significantly by osmolarity of reaction medium. These changes were associated with intracellular free calcium. PMNs exposed in hyposmotic medium generated AO, just as they were stimulated. However PMNs exposed in hyperosmotic medium did not generate AO. The stimulation-dependent AO generation of PMNs was increased in hyposmotic solution, while in PMNs incubated at 37 degrees C for 60 min in hyposmotic solution, this generation was decreased than controls. On the other hand, the stimulation-dependent generation was decreased in hyperosmotic solution, while incubated in hyperosmotic solution, this generation was increased. These results suggest that ability of urinary PMNs is regulated by urine osmolarity and retaining time or many other factors, however urinary PMNs are primed and maintain bactericidal activity.

Animals↗

PubMed2000

Does the generation effect occur for pictures?

The generation effect is the finding that self-generated stimuli are recalled and recognized better than read stimuli. The effect has been demonstrated primarily with words. This article examines the effect for pictures in two experiments: Subjects named complete pictures (name condition) and fragmented pictures (generation condition). In Experiment 1, memory was tested in 3 explicit tasks: free recall, yes/no recognition, and a source-monitoring task on whether each picture was complete or fragmented (the complete/incomplete task). The generation effect was found for all 3 tasks. However, in the recognition and source-monitoring tasks, the generation effect was observed only in the generation condition. We hypothesized that absence of the effect in the name condition was due to the sensory or process match effect between study and test pictures and the superior identification of pictures in the name condition. Therefore, stimuli were changed from pictures to their names in Experiment 2. Memory was tested in the recognition task, complete/incomplete task, and second source-monitoring task (success/failure) on whether each picture had been identified successfully. The generation effect was observed for all 3 tasks. These results suggest that memory of structural and semantic characteristics and of success in identification of generated pictures may contribute to the generation effect.

Adult↗

PubMed2000

Role of molecular oxygen in the generation of hydroxyl and superoxide anion radicals during enzymatic Cr(VI) reduction and its implication to Cr(VI)-induced carcinogenesis.

Electron spin resonance (ESR) spin trapping measurements provide evidence for the generation of hydroxyl radicals (*OH) in the reduction of Cr(VI) by glutathione reductase (GSSG-R) in the presence of NADPH as a cofactor. Catalase inhibited the *OH generation, while the addition of H2O2 enhanced it, indicating that the *OH radical generation involves a Fenton-like reaction. The metal chelator, deferoxamine, inhibited the *OH generation with a concomitant generation of a deferoxamine nitroxide radical. EDTA and 1,10-phenanthroline also inhibited the *OH generation. Experiments performed under argon atmosphere decreased the yield of the *OH formation, showing that molecular oxygen plays a critical role. ESR spin trapping and measurements of fluorescence change of scopoletin in the presence of horseradish peroxidase show that reduction of Cr(VI) by GSSG-R/NADPH generates superoxide anion radicals (O2*-) as well as H2O2. It can be concluded that *OH radical is generated by the reaction of H2O2 with Cr(V), which is produced by enzymatic one-electron reduction of Cr(VI). H2O2 is produced by the reduction of molecular oxygen via O2*- as an intermediate. The *OH radicals generated by these reactions are capable of causing DNA strand breaks, which can be inhibited by catalase, formate, and experiments performed under argon.

Carcinogenicity Tests↗