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PubMed2001

Heterogeneity and its biodemographic implications for longevity and mortality.

In the visible world, heterogeneity typically refers to the differences that exist among individuals in a defined population. These differences can arise from a variety of sources--biological, behavioral and social. Ever since Darwin, scientists have argued over the biological significance of differences observed at the individual, morphological, physiological, genetic, molecular and structural levels. A general consensus has been reached. Heterogeneity is ubiquitous, it is important, and it increases as observations are made at finer levels of biological resolution. Debates over the significance of heterogeneity have emerged once again as biologists and demographers work together in order to create the emerging field of biodemography. For these scientists, the debates center around the relative impact that individual heterogeneity has on population level statistics. It is argued here that in a world where the mortality barriers to long life for individuals have been dramatically weakened, the population consequences of heterogeneity are already visible and will grow in importance as biomedical technologies continue to usher progressively more people into the post-reproductive period of the lifespan.

Animals↗

PubMed1982

The effect of dietary restriction on cell division potential, DNA content and enzyme levels in the rotifer Asplanchna brightwelli.

Dietary restriction in the rotifer Asplanchna brightwelli, carried out by lengthening the interval between feedings, causes an increase both in mean lifespan and in the length of the reproductive period. In the present study, we found that the rate of nuclear division in the gastric glands and vitellarium of the rotifer, as determined by daily nuclear counts, was retarded by dietary restriction. Spectro-fluorimetric measurements show that total DNA content remains constant from the beginning to the end of the lifespan, and is unaffected by dietary restriction. Lactic dehydrogenase and malic dehydrogenase activities were also measured throughout the lifespan of the rotifer, and were not affected by dietary restriction.

Aging↗

PubMedDate not supplied

Lymphangioleiomyomatosis initially presenting with abdominal pain: a case report.

Lymphangioleiomyomatosis (LAM) is a rare idiopathic disease characterized by hamartomatous smooth muscle proliferation of the lymph node, lymphatics, blood vessels as well as airways within the lungs, mediastinum and abdomen. It exclusively affects women during the reproductive period. Though extrapulmonary manifestations have been reported, the initial presentation of LAM as abdominal pain is extremely rare. To our knowledge, there are only three cases with LAM presenting first with abdominal symptoms so far [Chest 106 (1994) 267; Eur J Radiol 14 (1992) 192; Eur J Surg 157 (1991) 36]. We describe a case of LAM suffering from abdominal pain followed by pulmonary symptoms and the diagnosis was not made until pathohistological examination.

Abdominal Neoplasms↗

PubMed2001

Gender differences in the efficacy of fluoxetine and maprotiline in depressed patients: a double-blind trial of antidepressants with serotonergic or norepinephrinergic reuptake inhibition profile.

BACKGROUND: Depression has emerged as a contrastive area of gender differences in psychiatry, as epidemiological data has consistently shown depression is twice as common in women as men. The pharmacodynamic effect of antidepressants may also show gender differences, as suggested by reports of better response of young women to non-tricyclic antidepressants. METHODS: The antidepressive effect of an SSRI (fluoxetine) and a tetracyclic antidepressant with selective norepinephrine reuptake inhibitory effect (maprotiline) was compared in a 6-week, double-blind trial of 105 depressed patients. RESULTS: No significant difference was observed in the change of HAMD17 total score from baseline to week 6 between fluoxetine- and maprotiline-treated patients. A significant difference was observed in females (fluoxetine, -17.8; maprotiline, -13.9; P=0.017) between treatment groups, but not in males. Amongst females, the difference was significant in women aged <44 years (fluoxetine, -18.4; maprotiline, -12.9; P=0.023) but not > or =44 years. CONCLUSIONS: Females in their reproductive period are more responsive to SSRI (fluoxetine) than norepinephrinergic tetracyclic antidepressant (maprotiline) treatment. Normal cyclical ovulation, and estrogen release may have a clinically relevant pharmacodynamic interaction with serotonergic antidepressants.

Adrenergic Uptake Inhibitors↗

PubMed1997

Ageing: levelling of the grim reaper.

Recent observations of a levelling of the death rate in extreme old age, in both experimental species and humans, are posing difficult problems for evolutionary biologists, in particular about the evolution of the post-reproductive period.

Aging↗

PubMed1987

Twinning in New England in the 17th-19th centuries.

Vital records of Saybrook and Plymouth in New England from the 17th century were investigated. Among 8,562 maternities 81 twin maternities were found, the twinning rate being 0.95%. Twinning rate was low at the 1st and 2nd births as compared with the 3rd or later births, and was highest at the 7th and 8th births (1.6%). Twin maternity seemed to be a strong risk factor to terminate reproduction, particularly after 6 or more children had been delivered. The rate of mothers who had any other child ("fertile" mothers) at the 7th or later birth order was significantly lower for twin (13%) than for singleton maternities (63%). Twinning rate also varied by the size of offspring of a mother, and those mothers who had 5 or 6 children showed the highest twinning rate (1.3%). Those fertile mothers who had 7 or more children showed the lowest twinning rate (0.74%), although an exceptionally higher twinning rate was seen at their last births. Elongation of the last birth interval was observed for each group of every family size, and higher twinning rates were generally observed at their last births. Reduction in fecundity and rise in twinning rate seem to have occurred simultaneously at the last stage of the reproductive period of mothers, regardless of their family size.

Birth Intervals↗

PubMed1996

Spontaneous maturation in Bufo arenarum oocytes: participation of protein kinase C.

Although progesterone is the maturation inducer in amphibians, it has been demonstrated that in Bufo arenarum oocytes resumed meiosis with no need of exogenous hormonal stimulus if derived of their enveloping follicle cells. This phenomenon, called spontaneous maturation, is quite rare in amphibians. In B. arenarum, spontaneous maturation took place only in oocytes obtained during the reproductive period (spring-summer). During this period the oocytes also demonstrated a respiratory activity characteristic of mature oocytes. Interestingly, full-grown B. arenarum oocytes always responded to progesterone regardless of the season in which they were obtained and of their respiratory activity. The disposition of oocytes competent or not competent to mature spontaneously provides a useful system for the study of molecular mechanisms involved in the maturation process. The data presented here indicate that the activation of protein kinase C (PKC) induces germinal vesicle breakdown (GVBD) in denuded oocytes unable to mature spontaneously (winter oocytes) and is involved in the in vitro spontaneous maturation of B. arenarum full-grown oocytes. The inhibition of PKC by 1-(5-isoquinolynyl-sulphonyl-2-methyl-piperazine (H-7) impeded spontaneous maturation in a dose-dependent manner, thus supporting the participation of the PKC pathway during this process. Interestingly phorbol 12-myristate-13-acetate (PMA)-induced GVBD is inhibited by the incubation of the oocytes in dibutyryl cAMP (dbcAMP), indicating that both pathways, PKC and protein kinase A (PKA), are related at a certain point. However, spontaneous GVBD is less sensitive than PMA-induced GVBD to dbcAMP. This fact would support the suggestion that in spontaneous GVBD mechanisms different from activation of PKC are at work.

Animals↗

PubMed2004

Effect of insulin on spontaneous and progesterone-induced GVBD on Bufo arenarum denuded oocytes.

Progesterone is considered as the physiological steroid hormone that triggers meiosis reinitiation in amphibian oocytes. Nevertheless, isolated oocytes can be induced to undergo germinal vesicle breakdown (GVBD) in a saline medium by means of treatment with various hormones or inducing agents such as other steroid hormones, insulin or an insulin-like growth factor. It has been demonstrated that Bufo arenarum oocytes obtained during the reproductive period (spring-summer) resume meiosis with no need of an exogenous hormonal stimulus if deprived of their enveloping follicle cells, a phenomenon called spontaneous maturation. This study was undertaken to evaluate the participation of the purine and phosphoinositide pathway in the insulin-induced maturation of oocytes competent and incompetent to mature spontaneously, as well as to determine whether the activation of the maturation promoting factor (MPF) involved the activation of cdc25 phosphatase in Bufo arenarum denuded oocytes. Our results indicate that insulin was able to induce GBVD in oocytes incompetent to mature spontaneously and to enhance spontaneous and progesterone-induced maturation. In addition, high intracellular levels of purines such as cAMP or guanosine can reversibly inhibit the progesterone and insulin-induced maturation process in Bufo arenarum as well as spontaneous maturation. Assays of the inhibition of phosphatidylinositol-4,5-bisphosphate (PIP2) hydrolysis and its turnover by neomycin and lithium chloride respectively exhibited a different response in insulin- or progesterone-treated oocytes, suggesting that phosphoinositide turnover or hydrolysis of PIP2 is involved in progesterone- but not in insulin-induced maturation. In addition, the inhibitory effect of vanadate suggests that an inactive pre-maturation promoting factor (pre-MPF), activated by dephosphorylation of Thr-14 and Tyr-15 on p34cdc2, is present in Bufo arenarum full-grown oocytes; this step would be common to both spontaneous and hormone-induced maturation. The data presented here strongly suggest that insulin initiates at the cell surface a chain of events leading to GVBD. However, our studies point to the existence of certain differences between the steroid and the peptide hormone pathways, although both involve the decrease in intracellular levels of cAMP, the activation of phosphodiesterase (PDE) and the activation of pre-MPF.

Adjuvants, Immunologic↗

PubMed1999

Comparative study of vitellogenesis in the anuran amphibians Ceratophrys cranwelli (Leptodactilidae) and Bufo arenarum (Bufonidae).

The present study analyses, by transmission electron microscopy, vitellogenesis in two anuran amphibian families: Leptodactilidae (Ceratophrys cranwelli) and Bufonidae (Bufo arenarum). These differ in the type of stimulus that sets off their reproductive period, pluvial changes being the trigger in C. cranwelli and temperature increase in B. arenarum. We found that vitellogenesis follows an endocytic pathway that involves membranous structures (coated pits, coated vesicles, endosomes and multivesicular bodies). This process results in a fully grown yolk platelet of similar structure in both species. Despite the above similarity, a distinctive feature in B. arenarum was that the multivesicular bodies exhibited condensed proteins together with lipid droplets, the latter remaining as such even in the primordial yolk platelet. In C. cranwelli, however, lipids droplets were only found attached to the primordial yolk platelet. The coexistence of lipid droplets together with proteins in the nascent precursor yolk platelets observed in B. arenarum is similar to that found in B. marinus. This fact might constitute a characteristic feature of the Bufonidae family.

Animals↗

PubMed2005

[Antidepressants and pregnancy].

Depressive disorders in women are not uncommon during the reproductive period. Identifying women at risk for the development of depression, early detection of depressive symptoms and an adequate treatment are important issues in preventing severe chronic depressive disorders. Do psychotherapeutic interventions not show any sufficient benefits, the use of antidepressants is indicated. In the meantime sufficient data are available concerning the use of anti-depressants during pregnancy to exclude any serious damage to the fetus or newborn. As a basic principle, a monotherapy should be favoured and the drug applicated in the lowest efficient dose. Due to the SSRI's side effect profile the choice of the antidepressant should be done in favour of serotonin reuptake inhibitors rather than tri- and tetracyclic antidepressants. For both substance groups there is no hint for any teratogenic potential. Benzodiazepine should be prescribed with caution. Negative long term effects to the newborn cannot be excluded. Based on few available data, indeed, there exists no reservation against the use of St. John's wort during pregnancy and breastfeeding. A profound ultrasound screening of the organs should be performed in case of lithium exposition, whereas newer studies showed no increase in risk for Ebstein anomaly. A multidisciplinary approach, including psychiatry, obstetrics and neonatology should be always aimed at in case of depressive disorders during pregnancy.

Antidepressive Agents↗

PubMed2001

Superior survival of blood and marrow stem cell recipients given maternal grafts over recipients given paternal grafts.

During the reproductive period, mothers and offspring exchange hematopoietic cells and develop a form of immunological tolerance bidirectionally. To examine whether previous experience of such communication has any remote effect when maternal hematopoietic cells are later transplanted to the children, we retrospectively compared the outcomes of blood and marrow stem cell transplantation from maternal donors (n = 46) to those from paternal donors (n = 50) by using the database of the Japanese nationwide surveys for adult hematopoietic cell transplants between 1990 and 1998. At 5 years, recipients of maternal hematopoietic cells had a significantly higher overall survival than patients receiving paternal grafts (60% vs 32%, P = 0.006). Although no significant difference was observed in the occurrence of severe acute GVHD (grade > or =III) and the relapse of malignant diseases between two groups, the probability of non-relapse treatment-related mortality was significantly lower after maternal donor transplants. Furthermore, multivariate analysis revealed that parental donor type was the only factor significantly associated with overall survival. In conclusion, our analysis indicates superior survival of maternally donated recipients in hematopoietic stem-cell transplantations from biological parents. This finding has important implications in the selection of alternative familial donors, and warrants further prospective analysis of parental donor transplantations.

Adolescent↗

PubMed1981

Effects of changes of photoperiod on gametogenesis in the rainbow trout (Salmo gairdneri).

After their first reproductive period, adult male and female rainbow trout were put under three different photoperiodic regimes between January and June: (1) short daylength (6 h of light/day), (2) decreasing daylengths (16L : 8D leads to 10L : 14D), (3) skeleton photoperiod consisting of short day-length (6L : 18D) with a one-hour flash at various times during the dark cycle in a decreasing daylength fashion (between 16L and 10L), i.e. at the end of the daylight period of the preceding group. The rearing temperature was 15 degrees C. After the fish were killed in June, it was found that decreasing daylength (group 2) had stimulated vitellogenesis. In that group, spermatogenesis was also highly stimulated in all the males, and some were in spermiation. No significant stimulation of vitellogenesis was observed in any of the groups of females which showed a follicular diameter of less than 1 mm. Spermatogenesis had not begun in any males of group 1 and 3 but the testicular cycle was slightly advanced in group 3 in which residual spermatozoa had disappeared from the lobules, while they still subsisted in group 2. The hypothesis proposing the present pattern of photosensitive phase, shifting between 16L and 10L (group 3) during the gametogenetic cycle, cannot explain the stimulatory effect of the decreasing photoperiod (group 1).

Animals↗

PubMed2001

Medicine may be reducing the human capacity to survive.

It appears that limited natural selection is taking place in populations of developed countries, since most individuals survive and have the full opportunity to reproduce. This paper addresses contemporary natural selection in a developed country (Australia) using the biological state index. Although the general context of this paper focuses on Australia it can be expected that most other first-world and/or developed countries follow a similar pattern. The findings of this study, that 98% of individuals survive through their reproductive period and have the full opportunity to reproduce, support predictions that natural selection has limited influence on the evolution of first-world populations. It appears that first-world populations may not be naturally well adapted to their environment but use medical treatments/technology to increase their survival capacity and maintain fitness. This has two apparent consequences. First, the fitness of individuals will decrease, since less favorable genes can accumulate in the population, and secondly, disease processes will remain fit as they adapt to the selective pressures exerted by medicine. If medical treatment becomes ineffective, extensive mortality is expected since fit disease processes will be unleashed on unfit human populations. It appears that a possible answer to these problems may be found in gene therapy.

Adolescent↗

PubMed1988

[The older primipara: labor induction and rigidity of the soft tissues].

Textbooks and literature reports frequently view the primipara of advanced age as a group being at increased risk of prolonged labor, dystocia, injuries to the birth canal and fetal distress. Particularly, a rigid cervix and reduced elasticity of the soft tissues of the birth canal are claimed responsible for these risks. Clinically, this view causes a higher frequency of operative deliveries in this group of primipara. The aim of the study was to evaluate the influence of a rigid cervix and/or reduced elasticity of the soft tissues in the birth canal on the course of labor. According to the definition of the FIGO we identified 201 primipara of advanced age as being more than 35 years old in our database. 5966 primipara (age 18-34) served as control. No significant difference was found in regard to Bishop score, progress of labor, vaginal and perineal lacerations, fetal distress and anaesthesia. However, the overall frequency of operative deliveries was increased from 27% to 58% in the primiparas of advanced age. In particular, the incidence of caesarean section increased from 11.5% to 39%. In 66% rigid tissues were called as one of the reasons for operative delivery in this group of aged primipara. However, our analysis of clinical variables does not support the notion that these women in general have an increased frequency of dystocia and/or a more rigid cervix and decreased elasticity of the birth canal. We feel that in a considerable number of patients, the concern of the obstetricians and the women in a safer and less painful delivery by caesarean section are reasons for these increased operative procedures at the end of the reproductive period.

Adult↗

PubMed1977

Immune surveillance against virus-induced tumors and nonrejectability of spontaneous tumors: contrasting consequences of host versus tumor evolution.

Spontaneous tumours are defined as tumors that develop in the absence of all experimental interference. In contrast to the widely documented, strong rejection reactions against most virus-induced tumors, spontaneous tumors evoke little or no detectable rejection reaction in intact or preimmunized syngeneic hosts. The difference can be viewed in relation to the contrasting natural history of the two conditions. Spontaneous tumors evolve in several steps, as a fule. "Tumor progression" is a microevolutionary process at the level of the somatic tissue where successive clonal variants replace each other. Each new variant gains the upper hand due to its greater independence of some restricting host mechanism. Independence of immune restrictions must be part of this process. Host selection for immune resistance apparently plays no major role here, presumably because most of the naturally occurring tumors arise after the host has passed the peak of its reproductive period. Protection against the oncogenic effects of ubiquitous tumor viruses is, on the other hand, the result of host selection for immune mechanisms favoring prompt rejection of virus-transformed cells. This is neither synonymous with nor related to protection against the viral infection per se, which is frequently successful and usually quite harmless. A certain relationship can be perceived between the degree of viral ubiquity and the strength of immune protection against the corresponding tumor cells. Natural selection for host recognition of commonly occurring, virally induced changes in neoplastic cell membranes can be surmised to occur, at least in part, by the fixation of appropriate immune responsiveness (Ir) genes. The role of Ir genes for tumor recognition can be approached by the genetic analysis of the F1 hybrid resistance effect. Unresponsiveness to spontaneous tumors may be overcome by target-cell modification, e.g., by chemical coupling, somatic cell hybridization, or viral "xenogenization".

Animals↗

PubMedDate not supplied

Metallothionein concentration in the mussel Mytilus galloprovincialis as a biomarker of response to metal contamination: validation in the field.

Mussels were translocated from a shell-fish breeding area (Sète, on the French Mediterranean coast) to sites exposed to trace element inputs in April 2000. They were recovered 3 months later. Whole soft tissues from all of the sites (n = 97) were analysed for arsenic, cadmium, chromium, copper, mercury, nickel, lead and zinc. Metallothioneins (MTs) were also measured in the digestive gland and in the remaining tissues (allowing calculation of whole soft tissue concentrations) at 22 of the 97 sites. MT concentrations in the digestive gland and the whole soft tissues were strongly correlated. The condition index varied with food availability at different sites. This did not influenced MT concentrations in the whole soft tissues, whereas the condition index was negatively correlated to trace element concentrations. A model is proposed to minimize this influence of condition. Metal concentrations adjusted using this model showed significant correlations with MT levels for those metals (cadmium, copper, nickel and zinc) that are known to bind to this protein, with the exception of mercury. Even in moderately contaminated sites, measurement of the MT level in the soft tissues of mussels was generally able to discriminate between different levels of contamination, allowing the use of a simplified procedure compared with dissection of the digestive gland. It is recommended to avoid translocation and sampling during the reproductive period, which is well documented for commercial species such as Mytilus sp.

Animals↗

PubMed1993

Cadmium-109 metabolism in mice. III. Organ retention in mice ovariectomized after experiencing multiple rounds of gestation and lactation.

Organ retention of 109Cd was studied in multiparous female mice 6 wk after ovariectomy or sham-control surgery. Females previously had experienced from three to five rounds of gestation/lactation during a maximum of 5 successive, 42-d reproductive periods. Throughout the experiment, mice were provided with tracer amounts of 109Cd in drinking water as well as stable Cd appropriate for the itai-itai experience in solid diets otherwise sufficient or deficient in nutrient quality. For sufficient-diet females, organ 109Cd content and concentration values were somewhat lower in the ovariectomized group compared to the sham control group. For deficient-diet females, the opposite trend occurred. When ovariectomized groups were compared with round 5 breeder groups of the same dietary experience, in almost all instances organ 109Cd content and concentration values were lower in the ovariectomized animals. Exceptions to this trend occurred in hepatic and especially renal tissues, where 109Cd concentrations were higher in the deficient-diet, ovariectomized group. Finally, when the deficient-diet, ovariectomized group was compared with its sufficient-diet counterpart, significantly higher 109Cd content values were found for liver, kidneys, and whole body (minus GI tract) in the former group. Conversely, when the same tissue content values were compared between the sham-control groups, differences without exception proved to be nonsignificant.

Administration, Oral↗

PubMed2003

The role of somatic and germline mutations in aging and a mutation interaction model of aging.

Mutations with a deleterious effect that is expressed after the average reproductive period are not effectively selected against and can accumulate in the germline. A conservative estimate is that at least 1-2% of new deleterious mutations affect some aspect of DNA replication, repair, or chromosome segregation. Since deleterious mutations can have an effect even as heterozygotes, this mutation accumulation can create an inherited background of late-acting mutations that themselves enhance mutation rate. This can have an interactive effect, in that it may increase the rate of somatic mutation during an individual's lifetime. The aging individual therefore becomes increasingly mosaic for somatic mutations, which in turn could potentially contribute to the gradual deterioration of biological processes and influence what we experience as senescence. Interventions that reduce somatic and germ cell mutations should, therefore, reduce the aging process in present and future generations.

Aging↗