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PubMed1984

Hydrocortisone suppresses the generation of nonspecific "anomalous" killers but not specific cytolytic T lymphocytes in human mixed lymphocyte-tumor cultures.

Interpretation of results with the use of effector populations generated in human mixed lymphocyte tumor cultures (MLTC) has in many cases been clouded by the presence of two distinct cytolytic effectors: specific cytolytic T lymphocytes (CTL) and nonspecific anomalous killers (AK). The addition of 5 to 50 X 10(-6) M hydrocortisone sodium succinate (HC) to "three-cell" allogeneic human MLTC containing responder lymphocytes, irradiated allogeneic glioma cells, and irradiated third-party stimulator lymphocytes consistently reduced the generation of AK by greater than 90% while having little or no effect on the generation of CTL specific for antigens present on the glioma cells. HC was similarly effective in blocking the generation of AK when added to cultures of responder cells incubated with lymphokine-containing supernatants from mixed lymphocyte cultures. Kinetic experiments indicated that HC both decreased the initial rate of appearance of AK activity and subsequently caused the AK response to decline more rapidly. HC had only a small inhibitory effect on the lytic action of AK generated in its absence. The ability of HC to suppress strongly the generation of nonspecific but not specific cytolytic effectors suggests that nonspecific AK are not polyclonally activated CTL or CTL at an early stage of differentiation, but rather represent a distinct cytolytic effector system. The inclusion of HC in human MLTC may provide a useful tool for distinguishing between lysis due to the generation of specific CTL and lysis due to the generation of nonspecific AK.

Antibodies, Monoclonal↗
PubMed1984

Heparan sulfate and dermatan sulfate inhibit the generation of thrombin activity in plasma by complementary pathways.

Heparan with a low affinity for antithrombin III has previously been demonstrated to inhibit thrombin generation in both normal plasma and plasma depleted of antithrombin III. In addition, standard heparin and heparin with a low affinity for antithrombin III have been demonstrated to have equivalent inhibitory actions on thrombin generation in plasma depleted of antithrombin III. These observations prompted the investigation of the effects of four normal vessel wall glycosaminoglycans (heparan sulfate, dermatan sulfate, chondroitin-4-sulfate, and chondroitin-6-sulfate) on the intrinsic pathway generation of thrombin and factor Xa and on the inactivation of thrombin and factor Xa in plasma. Heparan sulfate inhibited thrombin generation and accelerated the inactivation of added thrombin and factor Xa in normal plasma but not in antithrombin III-depleted plasma. In contrast, dermatan sulfate inhibited thrombin generation in both normal and antithrombin III-depleted plasma. In addition, heparan sulfate was an effective inhibitor of factor Xa generation, while dermatan sulfate was not. Neither chondroitin-4-sulfate nor chondroitin-6-sulfate inhibited the generation of thrombin or factor Xa nor did they accelerate the inactivation of factor Xa or thrombin by plasma. These results suggest that heparan sulfate acts primarily by potentiating antithrombin III, while dermatan sulfate acts by potentiating heparin cofactor II. The inhibition of thrombin generation by heparan sulfate and dermatan sulfate thus appears to occur by complementary pathways, both of which may contribute to the anticoagulation of blood in vivo.

Anticoagulants↗
PubMed1994

Generational analyses of suicide: baby boomers and 13ers.

"Generational analysis" is proposed that would consider actual cohort or generational suicide risk. Personality characteristics of different generations are discussed as they may affect suicide, its prevention, and intervention. In addition, annual suicide data for 1968-1991 are presented for the "Boom" generation (born 1943-1960) and for the young group of Americans called 13ers (the 13th generation of Americans; born 1961-1981). Results indicate that Boomers are presently 1 of every 3 suicides and 1 of every 4 Americans, while 13ers are 1 of 4 suicides and 1 of 3 in the population. Consistent with previous cohort analysis studies, these two cohorts are at greater risk than earlier generations at the same chronological age, with 13ers higher than Boomers for the ages they have thus far attained. It is recommended that researchers, theorists, and mental health professionals consider generational issues, and that suicidology expand its attention to the life cycles of generations.

Adolescent↗
PubMed1993

Thrombin generation during cardiac surgery: is heparin the ideal anticoagulant?

Blood samples were collected from 43 patients undergoing elective cardiac surgery to determine the extent of thrombin generation and inhibition in patients when receiving heparin while undergoing cardiopulmonary bypass (CPB). Plasma prothrombin fragment F1 + 2 and thrombin-antithrombin III (TAT) levels were measured as markers of thrombin generation and inhibition, respectively. Both F1 + 2 and TAT levels increased significantly during the course of CPB despite the heparin causing significant systemic anticoagulation, i.e. the activated coagulation time (ACT) was prolonged to greater than 400 s throughout the entire surgical procedure. The extent of thrombin generation increased with time on CPB but did not differ between patients receiving normothermic and hypothermic cardioplegia during CPB. Furthermore, thrombin generation increased following the neutralization of the heparin with protamine sulphate, and continued to be elevated significantly 24 h post surgery. The observation that high dose heparin did not prevent thrombin generation during CPB, is consistent with previous experimental studies demonstrating that thrombin bound to fibrin or other surfaces (e.g. the CPB conduit) is resistant to antithrombin III/heparin inhibition, and thus able to facilitate further thrombin generation. The observation that thrombin generation continued to be elevated post surgery i.e. 24 h after neutralizing the heparin with protamine sulphate, suggests that the high dose heparin did not inhibit effectively all of the thrombin that had been generated. Thus, CPB patients may be at risk not only of bleeding and other side-effects associated with the acute use of high dose heparin, but may also be at risk of further thrombosis-related events either acutely or chronically.

Aged↗
PubMed1998

The aqueous humor is capable of generating and degrading H2O2.

PURPOSE: To determine the ability of the aqueous humor to generate and degrade H2O2, the effect of environmental factors such as oxygen tension and temperature, and the constituents contributing to the observed results. METHODS: Aqueous humor was carefully removed from bovine eyes within 3 hours of death. Standard and new techniques were used to follow H2O2 degradation and formation. Catalase activity was measured by H2O2 decomposition, usually at 100 microM and 10 mM H2O2, and in some cases by O2 generation. RESULTS: Bovine aqueous humor generated and degraded H2O2. The generation of H2O2 was minimal at 0 degrees C but increased as temperature increased, so that at 37 degrees C at 3 hours, approximately 90 microM H2O2 was observed. Degradation was more complex. At 0 degrees C, only a slow rate of degradation was observed. At 25 degrees C, it was more rapid, and a steady state between generation and degradation was observed at approximately 30 microM. However, at 37 degrees C, starting with 100 microM H2O2, degradation was initially rapid, but then generation became predominant and H2O2, concentration increased to more than 100 microM in 3 hours. No H2O2 was generated in the absence of O2, and H2O2 production increased with increasing O2 tension. Both low and high molecular weight components contributed to the degradation, but synthesis was completely dependent on low molecular weight constituents. Ascorbic acid and metal ions such as Cu+ made a major contribution to H2O2 production. Catalase may be the macromolecular component responsible for aqueous H2O2 decay, as evidenced by H2O2 degradation, inhibition by boiling or 3-aminotriazole, and the approximate correspondence between oxygen generation and H2O2 degradation. CONCLUSIONS: The results indicate that the aqueous humor is capable of producing levels of H2O2 that have been shown previously to cause cataract in organ culture. Changes in aqueous humor metal ion content and concentration of oxygen level have profound effects on H2O2 concentration and may effect lens viability. The variation in published H2O2 levels may in part be the result of the conditions under which the aqueous humor was obtained, stored, and used for assay. The observed steady state H2O2 concentration of 1 microM in fresh aqueous from bovine eyes must be maintained by the metabolism of surrounding tissues as well as intrinsic components capable of degrading H2O2.

Animals↗
PubMed1998

Triumphant transitions: socioeconomic achievements of the second generation in Canada.

"Articulated within the last decade, the revisionary perspective on second generation integration argues that the model of equal or above average success of the second generation in North America is historically specific, based on the postwar entry of a white second generation in boom economic times. One implication is that the past patterns of second generation success may not hold now and in the future for immigrant offspring. Using data from the 1994 Canadian General Social Survey for women and men, age 25-64, this article assesses the proposition of triumphant transitions in which the second generation experiences high levels of educational and labor market achievements. Multivariate analyses confirm second generation success with respect to educational levels and occupational status, thus contradicting verdicts of a new chapter to be written for the second generation in Canada."

Acculturation↗
PubMed2005

Families at high and low risk for depression: a 3-generation study.

BACKGROUND: The familial nature of early-onset major depressive disorder (MDD) has been documented in numerous family studies of adults and is supported by studies of offspring of parents with MDD, for whom the risk is more than 3-fold. None of the published high-risk studies have gone beyond 2 generations, and few have a longitudinal design. We report results of an approximately 20-year follow-up of families at high and low risk for depression. The first 2 generations were interviewed 4 times during this period. The offspring from the second generation are now adults and have children of their own, the third generation of the original cohort. OBJECTIVE: To examine the familial aggregation of psychiatric disorders and functioning in grandchildren by their parents' and grandparents' depression status. DESIGN: Longitudinal, retrospective cohort, family study. PARTICIPANTS: One hundred sixty-one grandchildren and their parents and grandparents. MAIN OUTCOME MEASURES: Lifetime rate of psychiatric disorder and functioning in grandchildren, stratified by parental and by grandparental depression status, collected by clinicians blind to diagnoses of previous generations and to previous interviews. RESULTS: There were high rates of psychiatric disorders, particularly anxiety disorders, in the grandchildren with 2 generations of major depression, with 59.2% of these grandchildren (mean age, 12 years) already having a psychiatric disorder. The effect of parental depression on grandchildren's outcomes differed significantly with grandparental depression status. Among families with a depressed grandparent, increased risk of anxiety (relative risk, 5.17; 95% confidence interval, 1.4-18.7; P = .01) and increased risk of any disorder (relative risk, 5.52; 95% confidence interval, 2.0-15.4; P = .002) were observed in grandchildren with a depressed parent as compared with those with nondepressed parents. The severity of parental depression, as measured by impairment, significantly increased the rate of a mood disorder in these grandchildren (relative risk, 2.44; 95% confidence interval, 1.1-5.5; P = .03). In contrast, among grandchildren with nonfamilial depression, ie, depressed parents with no depressed grandparents, there was no significant effect of parental MDD on grandchildren diagnoses. However, parental MDD, regardless of whether families had a depressed grandparent, had a significant impact on the grandchildren's overall functioning. Potential confounding variables did not affect the strength of the association with parental and grandparental depression. CONCLUSIONS: The association between parental MDD and child diagnosis is moderated by grandparental MDD status. The rates of psychopathology are highest in grandchildren of parents and grandparents with a moderately to severely impairing depression. Anxiety disorders are the early sign of psychopathology in the young grandchildren. Early interventions in the offspring of 2 generations affected with moderately to severely impairing MDD seem warranted. This familial group may be the target for neuroimaging, genetic, and other biological studies.

Adult↗
PubMed2006

Identification of patients at low risk for recurrent venous thromboembolism by measuring thrombin generation.

CONTEXT: Screening of patients with venous thromboembolism (VTE) for thrombophilic risk factors is common clinical practice. Because of the large number of risk factors, assessing the risk of recurrence in an individual patient is complex. A method covering multicausal thrombophilia is therefore required. OBJECTIVE: To investigate the relationship between recurrence of VTE and a simple global coagulation assay measuring thrombin generation. DESIGN, SETTING, AND PARTICIPANTS: Prospective cohort study of 914 patients with first spontaneous VTE who were followed up for an average of 47 months after discontinuation of vitamin K antagonist therapy. The study was conducted at the Department of Internal Medicine I, Medical University of Vienna, Vienna, Austria, between July 1992 and July 2005. Thrombin generation was measured by a commercially available assay system. Patients with a previous or secondary VTE; antithrombin, protein C, or protein S deficiencies; presence of lupus anticoagulant; cancer; or pregnancy were excluded. MAIN OUTCOME MEASURE: Objectively documented symptomatic recurrent VTE. RESULTS: Venous thromboembolism recurred in 100 patients (11%). Patients without recurrent VTE had lower thrombin generation than patients with recurrence (mean [SD], 349.2 [108.0] nM vs 419.5 [110.5] nM, respectively; P<.001). Compared with patients who had thrombin generation greater than 400 nM, the relative risk (RR) of recurrence was 0.42 (95% confidence interval [CI], 0.26-0.67; P<.001) in patients with values between 400 nM and 300 nM; for patients with lower values, the RR was 0.37 (95% CI, 0.21-0.66; P = .001). After 4 years, the probability of recurrence was 6.5% (95% CI, 4.0%-8.9%) among patients with thrombin generation less than 400 nM compared with 20.0% (95% CI, 14.9%-25.1%) among patients with higher values (P<.001). Patients with thrombin generation less than 400 nM, representing two thirds of patients, had a 60% lower RR of recurrence than those with greater values (RR, 0.40; 95% CI, 0.27-0.60; P<.001). CONCLUSION: Measurement of thrombin generation identifies patients at low risk for recurrent VTE.

Adult↗
PubMed1997

Comparative analysis of the ability of precursor germ cells and epididymal spermatozoa to generate reactive oxygen metabolites.

Male germ cells at various stages of differentiation from pachytene spermatocytes to mature caudal epididymal spermatozoa were examined for their ability to generate reactive oxygen species (ROS) using sensitive chemiluminescence techniques. In general, spermatozoa were found to spontaneously generate hydrogen peroxide as they progressed through the epididymis, maximal activity being observed on the release of mature cells from the caudal region into a modified Krebs-Ringer's solution. The spontaneous production of hydrogen peroxide rose rapidly during the first 10 min after the spermatozoa had been diluted into culture medium and thereafter stabilized, neither phorbol esters nor A23187 subsequently influencing this activity. Low levels of superoxide generation were also detected in suspensions of epididymal spermatozoa, but did not correlate with maturation status. However, superoxide production could be dramatically enhanced by the addition of exogenous NADPH, in a manner that was closely correlated with the stage of epididymal development being maximal for immature cells recovered from the caput epididymis in all species. Precursor germ cells (pachytene spermatocytes, round and elongate spermatids) similarly generated chemiluminescent signals compatible with the low level generation of ROS. Superoxide generation in these cells could again be stimulated by NADPH, via mechanisms that were inversely related to the stage of germ cell differentiation, the greatest activity being observed in pachytene spermatocytes. These results demonstrate that differentiating male germ cells have the potential to generate ROS, and have implications for the redox regulation of gonadal function and the development of reproductive pathologies involving oxidative stress.

Animals↗
PubMed1997

Colorectal cancer risk in HNPCC families: development during lifetime and in successive generations. National Collaborative Group on HNPCC.

Members of hereditary non-polyposis colorectal cancer (HNPCC) families develop colorectal cancer at a much higher rate, and at a much younger age, than the general population. To quantify lifetime colorectal cancer risk in HNPCC family members, we calculated the cumulative incidence (CI) in different age categories, and compared this to the general population. Furthermore, we investigated whether successive generations of HNPCC families had earlier onset of disease. In 51 HNPCC families, selected according to the "Amsterdam criteria", the CI of colorectal cancer at age 75 was 40%, compared to only 4% in the general population. The CI ratio (CIR) of HNPCC family members relative to the general population was 148 at age 40, 79 at age 50 and 11 at age 75. Comparing successive generations of HNPCC families, the CI at age 75 increases from 19% in the ancestors to 32% in the first generation and 55% in the second generation. However, Cox proportional hazard analysis showed that this generation effect (RR per generation: 1.8, 95% CL = 1.4-2.2) largely disappears after adjustment for year of birth. In summary, at young ages, HNPCC family members experience an up-to-150 times higher risk for colorectal cancer than the general population. This risk difference declines from age 60 onwards. The earlier age of onset in successive HNPCC generations does not appear to be a biological feature of HNPCC, but reflects a secular time trend in cancer occurrence in these families, similar to that in the general population.

Adult↗
PubMed1996

Microglial lineage species are expressed in mammalian epidermal growth factor-generated embryonic neurospheres.

The epigenetic signals and progenitor cell species involved in progressive neural maturation in the mammalian brain are poorly understood. Although these complex developmental issues can be examined in cultures of generative zone progenitor cells, analysis of signaling relationships in complex progenitor cell systems requires the meticulous definition of the cellular complement at each developmental stage. The presence of microglia within the generative zone cultures would further complicate these developmental analyses. Utilizing the microglial markers Griffonia simplicifolia B4 isolectin, carbocyanine dye-acetylated low density lipoprotein, F4/80, and Mac-1 we now report the presence of microglia within cultures of late embryonic murine epidermal growth factor-derived generative zone progenitor cells. Cytokine treatment of serially passaged epidermal growth factor-generated neurospheres altered the phenotype of the microglia in culture. Macrophage colony-stimulating factor treatment promoted the expression of spindle-shaped microglia, whereas granulocytemacrophage colony-stimulating factor treatment promoted the elaboration of flat and amoeboid microglia. Treatment with microglial-conditioned medium or 10% non-heat inactivated fetal calf serum led to an increased complement of both phenotypes. Microglia could be generated from single isolated neurospheres, and there were differences in the number of microglial lineage species obtained from distinct oligopotent progenitor cells, raising the possibility that a complement of this cellular lineage may be derived from a progenitor cell present within the generative zones. These observations indicate that microglia are present within the generative zone progenitor cell system, and this system thus represents an important experimental resource to examine the progenitor cell maturation and the origin of the microglial lineage.

Animals↗
PubMed2002

Defective generation but normal maintenance of memory T cells in old mice.

The ability to maintain memory after encounter with antigen is one of the central features of the immune system. Immune memory generated during young age can be maintained well into old age. However, we know little about maintenance of immune memory generated during old age. In this study, we compared generation and maintenance of memory CD8 T cells in young (2-3-month-old) and aged (22-24-month-old) mice following acute lymphocytic choriomeningitis virus infection. We found that young mice made a more vigorous primary T cell response and generated higher levels of memory cells than old mice. However, once generated, memory CD8 T cells were maintained at stable levels in both young and old mice for more than 5 months. Interestingly, the generation of a secondary effector response in vivo was again slightly compromised in the old mice. Taken together, these results show that generation of T cell responses is compromised in old age, but maintenance of the pool of memory T cells is not affected by the aging process.

Aging↗
PubMed1994

Experimental grain dust atmospheres generated by wet and dry aerosolization techniques.

Properties of grain dust aerosols generated using wet and dry techniques were studied. Relative to the dry aerosol generation, the wet generation technique yielded a smaller particle size distribution (MMAED of 1.5 microns vs. 15.5 microns) but also reduced the viability of microorganisms. Analysis of dust mass and endotoxin activity on cascade impactor stages demonstrated equivalent partitioning of the airborne endotoxin with the dust mass for aerosols produced by either generation method. Comparison of laboratory-generated atmospheres to field sampling indicated a greater proportion of respirable microorganisms in soybean handling facilities than were generated using the dry aerosol system. Limitations of both aerosol generation systems were found that may affect the validity of inhalation toxicology studies in which these bioaerosols are artificially created.

Aerosols↗
PubMed2005

Two generation reproduction study of styrene by inhalation in Crl-CD rats.

This study was conducted to evaluate the potential adverse effects of styrene on reproductive capability from whole-body inhalation exposure of F0 and F1 parental animals. Assessments included gonadal function, estrous cyclicity, mating behavior, conception rate, gestation, parturition, lactation, and weaning in the F0 and F1 generations, and F1 generation offspring growth and development. Four groups of male and female Crl:CD(SD)IGS BR rats (25/sex/group) were exposed to 0, 50, 150, and 500 ppm styrene for 6 hr daily for at least 70 consecutive days prior to mating for the F0 and F1 generations. Inhalation exposure for the F0 and F1 females continued throughout mating and gestation through gestation day 20. Inhalation exposure of the F0 and F1 females was suspended from gestation day 21 through lactation day 4. On lactation days 1 through 4, the F0 and F1 females received styrene in virgin olive oil via oral gavage at dose levels of 66, 117, and 300 mg/kg/day (divided into three equal doses, approximately 2 hr apart). These oral dosages were calculated to provide similar maternal blood peak concentrations as provided by the inhalation exposures. Inhalation exposure of the F0 and F1 females was re-initiated on lactation day 5. Styrene exposure did not affect survival or clinical observations. Rats in the 150- and 500-ppm groups in both parental generations gained weight more slowly than the controls. There were no indications of adverse effects on reproductive performance in either the F0 or F1 generation. Male and female mating and fertility indices, pre-coital intervals, spermatogenic endpoints, reproductive organ weights, lengths of estrous cycle and gestation, live litter size and postnatal survival were similar in all exposure groups. Additionally, ovarian follicle counts and corpora lutea counts for the F1 females in the high-exposure group were similar to the control values. No adverse exposure-related macroscopic pathology was noted at any exposure level in the F0 and F1 generations. A previously characterized pattern of degeneration of the olfactory epithelium that lines the dorsal septum and dorsal and medial aspects of the nasal turbinates occurred in the F0 and F1 generation animals from the 500-ppm group. In the 500-ppm group, F2 birthweights were reduced compared to the control and F2 offspring from both the 150- and 500-ppm exposure groups gained weight more slowly than the controls. Based on the results of this study, an exposure level of 50 ppm was considered to be the NOAEL for F0 and F1 parental systemic toxicity; the NOAEL for F0 and F1 reproductive toxicity was 500 ppm or greater.

Animals↗
PubMed2004

Fermentation of biomass-generated producer gas to ethanol.

The development of low-cost, sustainable, and renewable energy sources has been a major focus since the 1970s. Fuel-grade ethanol is one energy source that has great potential for being generated from biomass. The demonstration of the fermentation of biomass-generated producer gas to ethanol is the major focus of this article in addition to assessing the effects of producer gas on the fermentation process. In this work, producer gas (primarily CO, CO(2), CH(4), H(2), and N(2)) was generated from switchgrass via gasification. The fluidized-bed gasifier generated gas with a composition of 56.8% N(2), 14.7% CO, 16.5% CO(2), 4.4% H(2), and 4.2% CH(4). The producer gas was utilized in a 4-L bioreactor to generate ethanol and other products via fermentation using a novel clostridial bacterium. The effects of biomass-generated producer gas on cell concentration, hydrogen uptake, and acid/alcohol production are shown in comparison with "clean" bottled gases of similar compositions for CO, CO(2), and H(2). The successful implementation of generating producer gas from biomass and then fermenting the producer gas to ethanol was demonstrated. Several key findings following the introduction of producer gas included: (1) the cells stopped growing but were still viable, (2) ethanol was primarily produced once the cells stopped growing (ethanol is nongrowth associated), (3) H(2) utilization stopped, and (4) cells began growing again if "clean" bottled gases were introduced following exposure to the producer gas.

Bioreactors↗
PubMed1998

Abnormally high nourishment during sensitive periods results in body weight changes across generations.

OBJECTIVE: This study asked whether a brief period of overnutrition during a developmentally sensitive time could impact the individual's adult weight and that of succeeding generations. RESEARCH METHODS AND PROCEDURES: Female rat pups (F1 generation) were randomly assigned to 1 of 3 groups: (1) a control group that was naturally reared by mothers; (2) another control group implanted with chronic gastric fistulas on postnatal day 4 and fed enough formula to match the growth of the mother-reared group; and (3) an experimental group gastrostomized and infused from day 8 through day 16 with a greater quantity of food than gastrostomy-reared controls (OF). On postnatal day 16, both gastrostomy-reared groups were returned to normal litters. Adult F1 females from overfed and mother-reared groups were bred with normal males to yield an F2 generation. F2 adult females were bred to normal males to produce an F3 generation. RESULTS: When adult, the F1 experimental group was heavier than control groups. F2 adults from OF mothers were smaller than those from the control group. F3 animals from OF grandmothers were heavier at weaning than F3 descendants from mother-reared animals. DISCUSSION: Excess nourishment during a developmentally sensitive period changed the metabolic phenotype of one generation so dramatically that the gestational development and subsequent phenotype of two succeeding generations were also changed. The experiment models fetal effects of gestational diabetes in humans and may help to elucidate how, independent of genetic anomalies, secular changes can be detected across generations.

Aging↗
PubMed1982

Combined two-generation reproduction-teratogenesis study of zearalenone in the rat.

The toxicity of zearalenone was studied in two generations of Wistar rats over approximately 10 months. Zearalenone was administered in the diet; the dose levels used were 0, 0.1, 1.0 and 10.0 mg per kg body weight per day in all generations. Animals in the F0 generation were bred twice to produce F1A and F1B generations. The F1A generation was bred to produce the F2A generation. The only lesion found at necropsy that could be attributed to zearalenone administration was increased medullary trabeculation of the femur in animals given the high dose. A dose-related increase in absolute and relative thyroid, pituitary and adrenal gland weights occurred in male and female rats of both the F1 and F1A generation. The alteration in the weights of these endocrine organs is probably a result of the estrogenic activity of zearalenone. Feeding of zearalenone caused decreases in fertility, number of viable offspring per litter and numbers of corpora lutea, implantations and resorptions per dam. Statistically significant differences were noted in the incidences of a number of skeletal and soft tissue abnormalities in both the F1B and F2A1 fetuses, especially at doses of 1.0 and 10.0 mg kg-1. These lesions most likely indicate a delay in fetal development. Unequivocal teratogenic effects could not be defined.

Abnormalities, Drug-Induced↗
PubMed2002

First-generation teeth in nonmammalian lineages: evidence for a conserved ancestral character?

The present study focuses on the main characteristics of first-generation teeth (i.e., the first teeth of the dentition to develop in a given position and to become functional) in representatives of the major lineages of nonmammalian vertebrates (chondrichthyans, actinopterygians, and sarcopterygians: dipnoans, urodeles, squamates, and crocodiles). Comparative investigations on the LM and TEM level reveal the existence of two major types of first-generation teeth. One type (generalized Type 1) is characterized by its small size, conical shape, atubular dentine, and small pulp cavity without capillaries and blood vessels. This type is found in actinopterygians, dipnoans, and urodeles and coincides with the occurrence of short embryonic periods in these species. The other type assembles a variety of first-generation teeth, which have in common that they represent miniature versions of adult teeth. They are generally larger than the first type, have more complex shapes, tubular dentine, and a large pulp cavity containing blood vessels. These teeth are found in chondrichtyans, squamates, and crocodiles, taxa which all share an extended embryonic period. The presence in certain taxa of a particular type of first-generation teeth is neither linked to their phylogenetic relationships nor to adult body size or tooth structure, but relates to the duration of embryonic development. Given that the plesiomorphic state in vertebrates is a short embryonic development, we consider the generalized Type 1 first-generation tooth to represent an ancestral character for gnathostomes. We hypothesize that an extended embryonic development leads to the suppression of tooth generations in the development of dentition. These may still be present in the form of rudimentary germs in the embryonic period. In our view, this generalized Type 1 first-generation teeth has been conserved through evolution because it represents a very economic and efficient way of building small and simple teeth adapted to larval life. The highly adapted adult dentition characteristic for each lineage has been possible only through polyphyodonty.

Animals↗