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PubMed1996

Nutrition knowledge and attitudes towards high-fat foods and low-fat alternatives in three generations of women.

OBJECTIVES: To assess family resemblance in food habits in three generations of maternally related family members. DESIGN AND SUBJECTS: Ninety-seven adult women, their mothers and grandmothers were asked about nutrition knowledge, attitudes and fat intake. Nutrition knowledge and attitudes were determined by means of a self-administered questionnaire. A food frequency questionnaire was used to assess fat intake. RESULTS: Mean percentage energy derived from fat was 39% for the younger generation, and 40% for their mothers and grandmothers. Generations differed in their nutrition knowledge score (P <0.0001), the grandmothers having a lower nutrition knowledge than the other generations. Correlations of nutrition knowledge scores were 0.30 (95% confidence limits (c.l.) 0.10 and 0.48) between the younger and middle generations, 0.35 (95% c.l. 0.16 and 0.52) between the middle and older generations, and 0.14 (95% c.l. -0.06 and 0.34) between the younger generation and their grandmothers. For attitudes towards high-fat foods and their low-fat alternatives these figures were 0.27 (95% c.l. 0.07 and 0.45), 0.22 (95% c.l. 0.01 and 0.41), and 0.17 (95% c.l. - 0.03 and 0.36), respectively, while for energy percentage of fat intake the correlations were only 0.19 (95% c.l. -0.01 and 0.37), -0.02 (95% c.l. -0.22 and 0.18), and 0.12 (95% c.l. limits - 0.08 and 0.31), respectively. Within generations the correlations between attitudes and nutrition knowledge or percentage energy derived from fat were found to be higher in the middle generation than in other generations. No statistically significant correlations were found between nutrition knowledge and percentage energy derived from fat. CONCLUSIONS: From this study it can be concluded that mothers and their adult daughters resemble each other in nutrition knowledge and attitudes.

Adult↗

PubMed1997

Regulation of neuroblast cell-cycle kinetics plays a crucial role in the generation of unique features of neocortical areas.

Cortical neurons are generated in the germinal zones lining the ventricles before migrating predominantly radially. To investigate regional differences in the cell-cycle kinetics of neuroblasts, pulse [3H]-thymidine injections were made throughout corticogenesis, and labeled neuron counts were compared in areas 3, 6, 17, and 18a in the adult mouse. The relationship between height in the cortex and intensity of autoradiographic signal distinguishes first generation and subsequent generations of neurons. This provides the mitotic history of defined sets of neurons and is a powerful tool for analyzing areal differences in cell-cycle kinetics. The infragranular laminar labeling indices of different generations show significant differences in areas 3 and 6. The labeling index of first generation neurons shows that the rate of neuron production is higher in area 3 than in area 6. This increased generation rate in area 3 was accompanied by two major changes. First, computation of the labeling index of the subsequent generation neurons (which reflects percentages of precursors in S-phase at the moment of the pulse) indicates a shorter cell cycle in area 3. Second, the total population of labeled neurons contains a higher proportion of first generation neurons in area 3, implying a higher leaving fraction in this area. Computer simulations of these areal differences of cell-cycle kinetics generate neuron numbers that are in close agreement with published data. Altogether these findings reveal an early regionalization of the ventricular zone that serves to generate unique features of future cortical areas.

Aging↗

PubMed1998

Cleavage requirements of factor V in tissue-factor induced thrombin generation.

Factor V (FV) activation is the result of cleavages at Arg709, Arg1018 and Arg1545 by thrombin or FXa. The relative importance of these cleavages in tissue factor (TF) induced thrombin generation in plasma and in a purified system was elucidated with recombinant FV in which the three sites had been eliminated one by one or in combinations. The mutants were analyzed with a clotting assay using FV-deficient plasma and in a TF induced thrombin generation system using plasma or purified components. Surprisingly, in the standard FV clotting assay, all mutants gave similar clotting activities and the thrombin generation curves obtained with wild-type and thrombin-resistant FV were similar. Differences in clotting activities and thrombin generation patterns between wild-type and thrombin-resistant FV were only observed when lower TF concentrations were used. The thrombin generation curve obtained in plasma containing wt FV was characterized by a short lag phase and a subsequent phase of rapid thrombin generation (propagation phase). The Arg709 to Gln mutation yielded a slightly prolonged lag phase and the rate of thrombin generation during the propagation phase was approximately 5-fold lower than that observed with wt FV. The Arg1018 to Ile mutation only slightly affected the thrombin generation curve, whereas the Arg1545 to Gln mutation yielded a prolonged lag phase and decreased maximum thrombin activity. Thrombin-resistant FV (mutated at all three sites) yielded a prolonged lag phase and poor thrombin generation during the propagation phase. The purified system further demonstrated the importance of the three cleavage sites for rapid and sustained thrombin generation. The results demonstrate that cleavages at positions 709, 1018 and 1545 are not required for assembly of a FXa-FV complex expressing low but significant prothrombinase activity but that all three sites in different ways are important for the creation of a FVa which maximally supports the FXa-mediated activation of prothrombin.

Arginine↗

PubMed1992

Immigration and immigrant generations in population projections.

This paper proposes a new model for population projections. This model projects an initial population under conditions of fertility, mortality, and international migration (like standard cohort-component models), but considers the population arrayed by generation. The model incorporates 4 generations: a foreign-born first generation (the immigrants), a second generation (sons and daughters of immigrants), a third generation (grandsons and granddaughters of immigrants), and fourth-and-higher generations. The model requires fertility, mortality, and migration equations by generation, which take a somewhat different form than in conventional cohort-component population projection. Consideration of the model also makes apparent that assignment of births to generations may not follow a simple form: the paper presents a method for including the empirical description of intergenerational births within the generational framework. As an example, the authors examine the next century of population growth for the Asian, Black, Hispanic, and White non-Hispanic populations in the US, comparing their growth rates and their composition within the total US population. With annual net immigration of 950,000, the total US population of 249 million in 1990 will top 400 million in 2070 and reach about 432 million in 2090. Thus, the level of immigration and emigration assumed in these projections suggests considerable population growth for the next hundred years. The racial/ethnic composition of the US will shift markedly during the next century, as described in the paper.

Americas↗

PubMed2026

Computed tomography-guided precision biopsy combined with metagenomic next-generation sequencing for etiological diagnosis in patients with blood culture-negative systemic infections.

ObjectiveTo evaluate the diagnostic efficacy of computed tomography-guided percutaneous biopsy combined with metagenomic next-generation sequencing in patients with blood culture-negative systemic infections and to assess the clinical impact of using this combined strategy for etiological confirmation and guidance of targeted antimicrobial therapy.MethodsThis single-center retrospective observational cohort study enrolled 78 patients who met the Sepsis-3 consensus criteria for suspected systemic infection and had negative conventional microbiological work-ups (at least two sets of blood cultures) between April 2022 and March 2025. All patients underwent computed tomography-guided biopsy of radiologically identified infectious foci, with specimens processed concurrently for conventional culture and metagenomic next-generation sequencing. Diagnostic performance was benchmarked against the final comprehensive clinical diagnosis, and the influence of metagenomic next-generation sequencing findings on antimicrobial therapy modification was analyzed. Sample size calculation, based on a prior study estimating an metagenomic next-generation sequencing detection rate of 85% (α = 0.05, β = 0.2), indicated a minimum of 68 cases; accordingly, 78 patients were enrolled.ResultsComputed tomography-guided biopsy was technically successful in all 78 patients (100%). The pathogen detection rate of metagenomic next-generation sequencing (91.0%, 71/78) was significantly higher than that of conventional culture (55.1%, 43/78; p < 0.001). Using the final clinical diagnosis as the reference standard, metagenomic next-generation sequencing achieved a sensitivity of 94.7% (95% confidence interval: 86.9-98.5), specificity of 100.0% (95% confidence interval: 29.2-100.0), positive predictive value of 100.0% (95% confidence interval: 94.9-100.0), and negative predictive value of 42.9% (95% confidence interval: 9.9-81.6). Among the 35 culture-negative specimens, metagenomic next-generation sequencing established a definitive microbiological diagnosis in 28 cases (80.0%) and detected polymicrobial infections in 11 cases (14.1% of the cohort). Antimicrobial therapy was rationally adjusted based on metagenomic next-generation sequencing results in 69.2% (54/78) of the patients.ConclusionsThe integration of computed tomography-guided precision biopsy with metagenomic next-generation sequencing offers a highly effective diagnostic approach for blood culture-negative systemic infections. This synergistic strategy improves etiological diagnosis by providing high-yield target specimens that enable comprehensive, unbiased pathogen screening, facilitates differentiation between infectious and non-infectious etiologies, and supplies critical evidence for guiding precision antimicrobial therapy. These findings highlight the growing role of interventional radiology in the contemporary framework of precision infectious disease management.

Humans↗

PubMed1997

Two-generation reproductive toxicity study of methyl tertiary-butyl ether (MTBE) in rats.

A two-generation reproductive toxicity study of methyl tertiary-butyl ether (MTBE) was conducted in Sprague-Dawley rats. Twenty-five rats of each sex (F0) were exposed by inhalation to 0, 400, 3000 or 8000 ppm MTBE vapor, 6 h a day for 10 weeks prior to mating. Parental animals were then mated within groups for up to 3 weeks. Parental females were exposed during mating, gestation and lactation (starting on day 5); parental males were exposed during mating through delivery of their last litter sired. The F1 adults were selected from the F1 litters and were exposed beginning on postnatal day 28 for at least 8 weeks before mating to produce F2 litters. During exposures to 3000 and 8000 ppm MTBE, group observations included hypoactivity and lack of startle reflex in parental animals from both generations. Parental animals at 8000 ppm were also ataxic. During the pre-mating period, body weights of the 8000 ppm males from both generations and the F1 females were significantly reduced compared to control animals. Transient body weight reduction was also observed in the 3000 ppm F1 males and females during the pre-mating period. Lactational body weights were increased in the 8000 ppm females from both generations. In the F1 generation, increased liver weights were noted in the 3000 and 8000 ppm animals for both sexes, although histopathological examination revealed no treatment-related effects. There were no treatment-related reproductive effects noted in any of the parameters measured in this study. Offspring survival was equivalent among treated and control groups from both generations, and there were no remarkable post-mortem findings. There was, however, a significant increase in dead F2 pups in the 8000 ppm group on postnatal day 4. The F1 litters at 3000 and 8000 ppm had lowered body weights from postnatal days 14-21 and 14-28, respectively. The F2 generation of pups at 3000 and 8000 ppm also exhibited lowered body weights from postnatal days 14-28 and 7-28, respectively. Body weight gains in both the F1 and F2 litters were also reduced for the corresponding time intervals. Thus, exposure to MTBE vapor produced no reproductive toxicity to two generations of Sprague-Dawley rats even in the presence of parental toxicity at 3000 and 8000 ppm. Postnatal toxicity was observed in the offspring of both generations, but only in the presence of maternal toxicity. The no-observed-effect level (NOEL) for both parental and postnatal toxicity is 400 ppm, and the NOEL for reproductive toxicity is at least 8000 ppm.

Administration, Inhalation↗

PubMed1998

The role of prescribing and referral bias in studies of the association between third generation oral contraceptives and increased risk of thromboembolism.

Recently published papers have shown a slightly increased risk for venous thromboembolism (VTE) among users of third generation oral contraceptive pills (OC) as compared with users of second generation OC. The extra risk is small (about twofold) and could be explained possibly by biases introduced into the original case-control studies. This paper examines the possible role of prescribing bias (i.e. that doctors would prescribe third generation OC preferentially to women whom they knew to be at risk of VTE) and referral bias (i.e. that doctors would preferentially refer women on third generation OC to hospital for investigations of symptoms suggestive of VTE). A cross-sectional survey was carried out of 106 physicians, to record their attitude to the prescription of OC in certain risk situations. Each doctor then extracted data on OC prescription from approximately 12 patients under his care. A total of 1192 patients were included. Data collected related to known risk factors to which the patient was prone, and the type of OC that the woman was taking. The results from the doctors' attitudinal survey showed that third generation oral contraceptives seemed to be very popular among doctors in England and that they would prefer to prescribe third generation to second generation oral contraceptives in virtually all risk situations, and also in situations where there was no particular risk of VTE. The results from the patients' survey, however, did not correspond with the attitudinal survey, and there was no evidence of a systematic bias running through this sample of patients, associating third generation OC prescription with particular risk factors. The results from the doctors' attitudinal survey on referral did not show any evidence of potential bias towards referring patients on third generation OC to hospitals. Comparison of this survey with an equivalent survey done in Germany suggests that there may be different factors governing doctors' behaviour in Germany and England, with reference to choice of OC prescription.

Journal Article↗

PubMed1988

Generation patterns of four groups of cholinergic neurons in rat cervical spinal cord: a combined tritiated thymidine autoradiographic and choline acetyltransferase immunocytochemical study.

This report examines the generation of cholinergic neurons in the spinal cord in order to determine whether the transmitter phenotype of neurons is associated with specific patterns of neurogenesis. Previous immunocytochemical studies identified four groups of choline acetyltransferase (ChAT)-positive neurons in the cervical enlargement of the rat spinal cord. These cell groups vary in both somatic size and location along the previously described ventrodorsal neurogenic gradient of the spinal cord. Thus, large (and small) motoneurons are located in the ventral horn, medium-sized partition cells are found in the intermediate gray matter, small central canal cluster cells are situated within lamina X, and small dorsal horn neurons are scattered predominantly through laminae III-V. The relationships among the birthdays of these four subsets of cholinergic neurons have been examined by combining 3H-thymidine autoradiography and ChAT immunocytochemistry. Embryonic day 11 was the earliest time that neurons were generated within the cervical enlargement. Large and small ChAT-positive motoneurons were produced on E11 and 12, with 70% of both groups being born on E11. ChAT-positive partition cells were produced between E11 and 13, with their peak generation occurring on E12. Approximately 70% of the cholinergic central canal cluster and dorsal horn cells were born on E13, and the remainder of each of these groups was generated on E14. Other investigators have shown that all neurons within the rat cervical spinal cord are produced in a ventrodorsal sequence between E11 and E16. In contrast, ChAT-positive neurons are born only from E11 to E14 and are among the earliest cells generated in the ventral, intermediate, and dorsal subdivisions of the spinal cord. However, all cholinergic neurons are not generated simultaneously; rather their birthdays are correlated with their positions along the ventrodorsal gradient of neurogenesis. The fact that large motoneurons and medium-sized partition cells are born before small central canal cluster and dorsal horn cells would appear to support the generalization that large neurons are generated before small ones. However, the location of spinal cholinergic neurons within the neurogenic gradient seems to be more importantly associated with the time of cell generation than somal size. For example, when large and small motoneurons located at the same dorsoventral spinal level are compared, both sizes of cells are generated at the same time and in similar proportions.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1991

Generation patterns of immunocytochemically identified cholinergic neurons at autonomic levels of the rat spinal cord.

The time at which a neuron is "born" appears to have significant consequences for the cell's subsequent differentiation. As part of a continuing investigation of cholinergic neuronal development, we have combined ChAT immunocytochemistry and [3H]thymidine autoradiography to determine the generation patterns of somatic and autonomic motor neurons at upper thoracic (T1-3), upper lumbar (L1-3), and lumbosacral (L6-S1) levels of the rat spinal cord. Additionally, the generation patterns of two subsets of cholinergic interneurons (partition cells and central canal cluster cells) were compared with those of somatic and autonomic motor neurons. Embryonic day 11 (E11) was the first day of cholinergic neuronal generation at each of the three spinal levels studied, and it also was the peak generation day for somatic and autonomic neurons in the upper thoracic spinal cord. The peak generation of homologous neurons at upper lumbar and lumbosacral spinal levels occurred at E12 and E13, respectively. Somatic and autonomic motor neurons were generated synchronously, and their production at each rostrocaudal level was virtually completed within a 2-day period. Cholinergic interneurons were generated 1 or 2 days later than motor neurons at the same rostrocaudal level. In summary, the birthdays of all spinal cholinergic neurons studied followed the general rostrocaudal spatiotemporal gradient of spinal neurogenesis. In addition, the generation of cholinergic interneurons also followed the general ventrodorsal gradient. In contrast, however, autonomic motor neurons disobeyed the rule of a ventral-to-dorsal progression of spinal neuronal generation, thus adding another example in which autonomic motor neurons display unusual developmental patterns.

Acetylcholine↗

PubMed2006

Neural activity related to self- versus externally generated painful stimuli reveals distinct differences in the lateral pain system in a parametric fMRI study.

Self-generated sensory stimulation can be distinguished from externally generated stimulation that is otherwise identical. To determine how the brain differentiates external from self-generated noxious stimulation and which structures of the lateral pain system use neural signals to predict the sensory consequences of self-generated painful stimulation, we used functional magnetic resonance imaging to examine healthy human subjects who received thermal-contact stimuli with noxious and non-noxious temperatures on the resting right hand in random order. These stimuli were internally (self-generated) or externally generated. Two additional conditions served as control conditions: to account for stimulus onset uncertainty, acoustic stimuli preceding the same thermal stimuli were used with variable or fixed delays but without any stimulus-eliciting movements. Whereas graded pain-related activity in the insula and secondary somatosensory cortex (SII) was independent of how the stimulus was generated, it was attenuated in the primary somatosensory cortex (SI) during self-generated stimulation. These data agree with recent concepts of the parallel processing of nociceptive signals to the primary and secondary somatosensory cortices. They also suggest that brain areas that encode pain intensity do not distinguish between internally or externally applied noxious stimuli, i.e., this adaptive biological mechanism prevents harm to the individual. The attenuated activation of SI during self-generated painful stimulation might be a result of the predictability of the sensory consequences of the pain-related action.

Adult↗

PubMed1995

Superoxide anion generation by human peripheral blood mononuclear cells in response to prothymosin alpha.

The ability of human peripheral blood mononuclear cells to respond to highly purified prothymosin alpha by generating superoxide anion was investigated. The generation of superoxide anion was detected by measuring the superoxide dismutase-inhibitable reduction of oxidized cytochrome C. Prothymosin alpha was shown to stimulate weakly these cells. The dose-response curve displayed a biphasic bell-shaped superoxide generation profile with two specific concentration optima for each individual blood donor, but with variations in optimal concentrations between the donors. By using a counter current centrifugation (elutriation) system, the mononuclear cell population was separated into several fractions according to their volume and density. Selective stimulation of these fractions with prothymosin alpha revealed that different cell populations were responsible for the generation of superoxide at higher and lower concentrations of stimulant, respectively. The response to the stimulus was immediate and lasted for a time period of about 4 to 8 min during which approximately 0.7 nmol O2- per min/10(6) cells were generated. The superoxide generation was cell-number-dependent with an optimum at 1 x 10(6) cells and lower rates for both smaller and larger cell numbers. Staurosporine, a potent inhibitor of protein kinase C, at concentrations sufficient to inhibit totally PMA-induced O2- generation, failed to affect the response of the cells to prothymosin alpha, while chelation of the extracellular Ca2+ abolished the lower but not the higher peak of O2- generation. Finally, simultaneous addition of prothymosin alpha and PMA resulted in a approximately 40% decrease of the O2- generation induced by PMA alone. A putative role as cell injury indicator is proposed for prothymosin alpha.

Cell Separation↗

PubMed1997

Significant levels of oxidants are generated by isolated cardiomyocytes during ischemia prior to reperfusion.

Oxidants such as reactive oxygen species (ROS) have been shown to participate in myocardial ischemia/reperfusion injury. While many studies report a burst of ROS at reperfusion, few reports have presented evidence of significant ROS generation during ischemia. Our previous studies of cultured cardiomyocytes indicated that antioxidants are most effective when given prior to reperfusion during ischemia. Therefore, we hypothesized that significant ROS generation may occur during ischemia prior to reperfusion. We tested this in a perfused isolated cardiomyocyte system (i.e. without neutrophils, endothelial cells, or xanthine/xanthine oxidase) during simulated ischemia/reperfusion while measuring oxidant generation using intracellular fluorescent probes. During ischemia, the ROS probes dihydroethidium and 2',7'-dichlorofluorescin were significantly oxidized, suggesting superoxide and H2O2 generation. At reperfusion following 1 h ischemia, these probes suggested a further burst of H2O2 and hydroxyl radicals. The antioxidants 2-mercaptopropionyl glycine and 1,10-phenanthroline used during ischemia attenuated oxidant generation, increased cell viability, and improved return of contraction after ischemia. To further evaluate the relationship between residual O2 and ROS generation, we administered O2 scavengers during ischemia and measured corresponding changes in oxidant generation, cell viability and contraction during reperfusion. Enzymatic scavenging of residual O2 during ischemia (reducing PO2 from 3.5 to 2.5 tau) paradoxically improved subsequent viability and contraction. These results indicate that cultured cardiomyocytes generate significant ROS during ischemia. This ROS generation is related to residual O2 present during ischemia and contributes significantly to the cellular injury seen at reperfusion.

Animals↗

PubMed1992

Improved detection of antibodies to hepatitis C virus using a second generation ELISA.

A screening assay for the detection of antibodies to hepatitis C virus (HCV); ORTHO HCV ELISA Test System, Second Generation, was compared with the currently licensed c100-3 based test (ORTHO HCV ELISA Test System). The second generation ELISA differs from the c100-3 based assay in that it detects circulating antibodies to both structural (nucleocapsid) and non-structural (NS3/NS4) HCV proteins. Specimens tested consisted of a cohort of 35 patients diagnosed with non-A, non-B hepatitis (NANBH) and 3971 presumably healthy volunteer blood donors. Second generation ELISA demonstrated significantly greater clinical sensitivity in patients with acute phase NANBH (80% vs. 60%) as well as chronic disease (88% vs. 72%). Additional specimens reactive only in second generation ELISA, demonstrated reactivity to HCV antigens c33c and/or c22-3 in supplemental testing by the Chiron HCV RIBA Assay System. The second generation ELISA also detected additional RIBA reactive volunteer blood donors (0.18% of the population tested) that were nonreactive in first generation ELISA. This data indicated that second generation ELISA would detect approximately 2 additional anti-HCV reactive donors per 1,000 screened. Specificities obtained with this low risk population were 99.6% for first generation and 99.7% for second generation ELISA.

Blood Donors↗

PubMed1987

Effects of angiotensin I converting enzyme (ACE) related substances upon the vascular prostacyclin generation.

We investigated the interaction of angiotensin I (AI) converting enzyme (ACE) related substances to prostacyclin (PGI2) generation and ACE activity using cultured human vascular endothelial cells (EC) and rat aortic rings (AR). In case of cultured EC, AI and bradykinin (BK) increased PGI2 generation and at the same time ACE released from EC, however angiotensin II (AII) did not show any effect on both of them. When the EC were pretreated by captopril both of basal PGI2 production and ACE activity were reduced but the enhancing effects on PGI2 generation by AI or BK were preserved. On the other hand in the experimental system with AR, not only AI or BK but also AII increased PGI2 generation and the higher concentration of captopril inhibited PGI2 generation. When the EC were removed, the enhancing effect by AII was diminished and the mechanical stimulation to AR remarkably increased PGI2. From these experimental studies, we obtained the results that (1) the reported hypothesis that the vasodilative effect of captopril would be developed by the enhanced PGI2 generation was not confirmed in our systems of EC and AR. (2) AII did not affect on PGI2 generation of EC. Therefore the enhanced PGI2 generation by AII in AR was considered to be mainly derived from the mechanical stimulation to EC by the AII induced smooth muscle cells contraction. (3) It was speculated that the enhanced PGI2 generation by AI or BK might be modulated through their activating effect on ACE as an autoregulatory mechanism.

Angiotensin I↗

PubMed1981

Genetically associated similarities and differences in the generation of neurons comprising an early developing reflex pathway in mouse spinal cord.

Tritiated thymidine autoradiography has been used to study the generation of lateral motor neurons (LMNs), association interneurons (ANs) and dorsal root ganglion cells (DRGNs) in the spinal cords of genetically diverse strains of mice. The neuronal populations analyzed in this study form an early developing reflex pathway and the ontogeny of this circuit exhibits genetically associated variability. The strains of mice used in this investigation have been shown to differ in the embryonic age at which forelimb reflex movements are first manifest and in the timing of synapse formation within the reflex pathway. A precocious development of these reflex traits occurs in strain C57BL/6J in comparison to embryos of intermediate (CBA/CaJ) and late developing (LP/J) strains. All three inbred strains show the same basic generation sequence for the neuronal populations comprising the forelimb reflex pathway. The generation of LMNs precedes that of ANs, and the generation of ANs, in turn, precedes that of DRGNs. Since this is the same sequence as that observed for the formation of synaptic junctions in all three strains, it is suggested that synaptogenic sequences in reflex circuits may be determined by the generation sequence of the component neuronal populations. Although the strains all exhibit the same basic sequence of neuronal generation, the temporal relationships of the generation of each cell population within this sequence show significant strain dependent variations. C57BL/6J displays a larger temporal separation between the generation of each cell type than LP/J, and CBA/CaJ is intermediate to the other two strains in this respect. The fact that this strain order is identical to that observed for the development of reflex traits suggests that genetically associated differences in the timing of neuronal birthdays within a common generation sequence may have a substantial influence on the timing of synaptogenesis within the reflex pathway.

Animals↗

PubMed2002

Suicide in first- and second-generation immigrants in Sweden: a comparative study.

BACKGROUND: Studies of suicide in first-generation immigrants have consistently shown higher rates compared to their country of origin. Little is known about the risk of suicide in second-generation immigrants and intercountry adoptees. The aim of this study was to investigate rates of suicide death in second-generation immigrants and intercountry adoptees in comparison with their parental generation and the majority population. METHOD: The study was based on multivariate analyses of register data on suicide death during 1990-98 in a Swedish national cohort of 2.7 million residents (10-68 years). RESULTS: Second-generation immigrants tended to have higher odds than the first-generation immigrants compared to the majority population in all six minority groups studied. The Finnish minority had the highest and the Middle Easterners the lowest odds for suicide death in both generations of immigrants. The intercountry adoptees had very high odds for suicide death (adjusted OR: 5.0; 95 % CI 3.5-7.0). CONCLUSIONS: Second-generation immigrants are at greater risk for suicide death than their parental generation. Intercountry adoptees should be of particular concern in suicide prevention.

Cohort Effect↗

PubMed1998

Limited importance of CD40/CD40L interaction in the B7-dependent generation of anti-MOPC-315 cytotoxic T lymphocyte activity by tumor bearer splenic cells stimulated in vitro in the presence of tumor necrosis factor.

We have previously illustrated the importance of B7-2 expression for the enhanced generation of cytotoxic T lymphocyte (CTL) activity by stimulation cultures of tumor bearer splenic cells to which tumor necrosis factor alpha (TNFalpha) has been added. Here we show that the B7-1 molecule is also important for CTL generation by such stimulation cultures, although to a much lesser extent than the B7-2 molecule. In addition, we show the importance of CD40/CD40L interaction for the expression of the B7-2 molecule, but not the B7-1 molecule, by tumor bearer splenic cells stimulated in vitro in the presence of TNF. The CD40/CD40L interaction is also shown to be important for the generation of CTL activity by tumor bearer splenic cells stimulated in vitro in the presence of exogenous TNF. However, the CD40/CD40L interaction is less important for the generation of enhanced CTL activity than for the expression of an elevated level of B7-2. Specifically, blockade of CD40/CD40L interaction, which reduced the level of B7-2 expressed by tumor bearer splenic cells stimulated in vitro in the presence of TNF to the level of B7-2 expressed by tumor bearer splenic cells stimulated in vitro in the absence of exogenous TNF, failed to reduce the level of CTL generated to the level generated by tumor bearer splenic cells stimulated in the absence of exogenous TNF. Finally, blockade of CD40/CD40L interaction was inferior to blockade of B7-2/CD28 interaction in inhibiting the generation of CTL activity by tumor bearer splenic cells stimulated in the presence of exogenous TNF. Thus, although CD40/CD40L interaction is important for the generation of enhanced CTL activity by stimulation cultures of tumor bearer splenic cells to which TNF has been added, TNF also mediates its potentiating effect for CTL generation by such stimulation cultures via other mechanisms that are independent of CD40/CD40L interaction but dependent on B7-2 expression.

Animals↗

PubMed1989

Generation of hydrogen peroxide by brain mitochondria: the effect of reoxygenation following postdecapitative ischemia.

The hypothesis that mitochondria damaged during complete cerebral ischemia generate increased amounts of superoxide anion radical and hydrogen peroxide (H2O2) upon postischemic reoxygenation has been tested. In rat brain mitochondria, succinate supported H2O2 generation, whereas NADH-linked substrates, malate plus glutamate, did so only in the presence of respiratory chain inhibitors. Succinate-supported H2O2 generation was diminished by rotenone and the uncoupler carbonyl cyanide m-chlorphenylhydrazone and enhanced by antimycin A and increased oxygen tensions. When maximally reduced, the NADH dehydrogenase and the ubiquinone-cytochrome b regions of the electron transport chain are sources of H2O2. These studies suggest that a significant portion of H2O2 generation in brain mitochondria proceeds via the transfer of reducing equivalents from ubiquinone to the NADH dehydrogenase portion of the electron transport chain. Succinate-supported H2O2 generation by mitochondria isolated from rat brain exposed to 15 min of postdecapitative ischemia was 90% lower than that of control preparations. The effect of varying oxygen tensions on H2O2 generation by postischemic mitochondrial preparations was negligible compared with the increased H2O2 generation measured in control preparations. Comparison of the effects of respiratory chain inhibitors and oxygen tension on succinate-supported H2O2 generation suggests that the ability for reversed electron transfer is impaired during ischemia. These data do not support the hypothesis that mitochondrial free radical generation increases during postischemic reoxygenation.

Animals↗