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Genome-Wide Mining of lncRNAs Reveals Their Potential Regulatory Role in the Evolution of Viviparity.

Reproduction in vertebrates usually involves egg-laying (oviparity) or live-bearing (viviparity). Oviparity is the ancestral trait from which viviparity has independently evolved more than 100 times in squamate reptiles. This transition involves a series of physiological and structural changes, including the degeneration of eggshell and the evolution of a placenta and differences in the temporal and spatial expression patterns of some functional genes that drive the structural transformation. Long non-coding RNAs (lncRNAs) play important roles in the regulation of gene expression, yet it remains unclear whether they participate in gene expression shifts during the transition from oviparity to viviparity, and if so how. Therefore, we employ deep mining to identify novel lncRNAs of a closely related oviparous-viviparous pair of lizards (Phrynocephalus przewalskii and P. vlangalii). We construct cis- and trans-regulatory networks between lncRNAs and target genes using the transcriptomic data of oviduct or uteri tissues across reproductive periods. Results show that lncRNAs that regulate eggshell gland developmental genes in the oviparous lizard are lost or less expressed in the viviparous lizard. A number of lncRNAs involved in the regulation of placental development and embryo attachment in viviparous species have no orthologs in oviparous species, and others show little or no expression. Accordingly, lncRNAs may play important regulatory roles in the physiological and structural changes in the transition from oviparity to viviparity. These results open doors to the further elucidation of genetic regulatory networks.

Animals↗

The clinical course of Behçet's disease in pregnancy: a retrospective analysis and review of the literature.

Although Behçet's disease is mainly diagnosed during the reproductive periods of life, we know little about the influence of pregnancy on the clinical course of Behçet's disease. Therefore, we analyzed the relationship between Behçet's disease and pregnancy retrospectively, in order to detect any possible interaction between the two multisystemic processes, particularly in regard to the influence of pregnancy on the clinical course of Behçet's disease. We studied 44 pregnancies in 28 women with Behçet's disease. The diagnoses were made according to the criteria of the International Study Group for Behçet's disease. The patients were observed during pregnancy and puerperium periods at monthly intervals. The existence and incidence of symptoms were recorded during these periods. There was remission of Behçet's disease during 23 (52.3%) pregnancies, although the disease had been in a stage of exacerbation before pregnancy. The disease became exacerbated during 12 (27.3%) pregnancies, although it had been in a stage of remission before pregnancy. There were no changes in the clinical course of Behçet's disease in 9 (20.4%) pregnancies. The most frequent manifestations of the clinical exacerbation were increases in the intensity and severity of outbreaks of oral ulcers during pregnancy. Outbreaks of genital ulcers, eye inflammations, and arthritis were other signs of exacerbation. Other than spontaneous abortion in three patients, we did not observe maternal or fetal complications. Although Behçet's disease tends toward remission during pregnancy, the influence of pregnancy on its clinical course is quite variable between patients and even during different pregnancies in the same patient. On the basis of our and previous results, we speculate that pregnancy in general does not seem to markedly affect the natural course of Behçet's disease.

Adolescent↗

Acquired symmetrical dermal melanocytosis (naevus of Hori) developing after aggravated atopic dermatitis.

BACKGROUND: Acquired symmetrical dermal melanocytosis (ASDM) is a pigmentary disorder characterized by blue-brown macules most frequently seen on the face of young and middle-aged Asian women. ASDM developing after other skin diseases has not been previously reported. OBJECTIVES: To characterize the clinical and histopathological features of ASDM associated with atopic dermatitis (AD) and to elucidate the differences between AD-associated ASDM and idiopathic ASDM. METHODS: Sixteen patients with ASDM associated with AD were examined clinically and histopathologically and were compared with 69 patients with idiopathic ASDM. RESULTS: The AD patients associated with ASDM consisted of four men and 12 women with a mean age of 32.8 +/- 13.1 years. Most patients remembered that the pigmented macules appeared in places where refractory eczema had existed for a long time. The marked preponderance in females and the appearance in the early reproductive period were common features of AD-associated ASDM and idiopathic ASDM. AD-associated ASDM was most commonly observed on the forehead (68.8%) and on the backs of the hands (50.0%), whereas 89.9% of idiopathic ASDM was seen on the cheeks. There was no significant difference in the number of dermal melanocytes between AD-associated ASDM and idiopathic ASDM. Electron microscopic studies demonstrated many mature melanocytes and smaller numbers of immature melanocytes in the dermis. Some melanocytes were seen adjacent to mast cells. CONCLUSIONS: AD-associated ASDM does not appear to be rare in Japan. ASDM may be triggered in AD patients by sunlight exposure, some alterations in sex hormones and/or persistent cutaneous inflammation. Histamine and stem cell factor produced by mast cells may play crucial roles in the pathogenesis of AD-associated ASDM.

Adult↗

Reconstitution of a human immune system in immunodeficient mice: models of human alloreaction in vivo.

Rodents have been widely used for studies in transplantation immunology because of their short reproduction period and the relative ease of generating inbred mutant or transgenic strains. However, although many biological mechanisms are similar between rodents and humans, several features clearly distinguish the immune system in these species. Consequently, it is rarely possible to extrapolate observations from rodent models directly into clinical practice. In vitro studies with human cells are useful for elucidation of basic mechanisms, but in order to study complex biological phenomena, in vivo studies are indispensable. In later years, a number of interesting models have been described where immunodeficient mice have been reconstituted with human cells, so-called humanized mice, in order to study human immune responses in vivo. This has opened a new field of experimental immunology that has been applied to areas such as cancer, autoimmunity, allergy, infections, and transplantation biology. In this review, we shall concentrate on the use of severe combined immunodeficient mice reconstituted with human immune or stem cells for studies of human alloreaction in vivo.

Animals↗

31P-nuclear-magnetic-resonance study of muscles from Mytilus edulis.

Phosphorus-31 nuclear magnetic resonance (NMR) spectra were recorded from freshly excised and resting anterior byssus retractor muscles of the mussel Mytilus edulis. The absolute concentrations of phosphometabolites measured by NMR compare well with the values obtained by a biochemical method. Quantitative measurements were achieved in several minutes by applying to the observed NMR signals a correction taking the saturation effects into account. The time evolution of the phosphometabolite concentrations reveals that the hydrolysis of phosphoarginine is a first-order reaction producing inorganic phosphate, whilst the adenosine triphosphate level remains constant for more than 10 h. The phosphoarginine hydrolysis rate varies as a function of the season and reaches a maximum during the reproduction period of the mussel. This increase in phosphoarginine consumption could be bound up with the higher excitability of the muscles during spring. The activation energy of the phosphoarginine hydrolysis reaction also depends on the season and the difference between the value determined in winter and that measured in spring is explained by a modification of the mode of action or of the proportions of the enzymes involved in the muscular metabolism.

Adenosine Triphosphate↗

Hereditary hemorrhagic telangiectasia with malignant lymphoma. An autopsy case.

A 60-year-old Japanese woman was diagnosed at autopsy as having had hereditary hemorrhagic telangiectasia (HHT) associated with systemic hemangiomas. In her reproduction period, premenstrual epistaxis frequently occurred. At the age of 60, the patient died of malignant lymphoma. At autopsy, multiple telangiectatic spots were noted on the face, limbs and trunk. The paraaortic lymph nodes, which were enlarged and irregularly conglomerated, were histologically diagnosed as malignant lymphoma of the diffuse large cell type. Submucosal telangiectatic lesions were found in the gastrointestinal system from the oral cavity to the rectum. Cavernous hemangiomas were present in various visceral organs including the liver, spleen, small and large intestines, rectum, appendix, uterus, and jejunal and colonic mesenteries. There was an arteriovenous fistula in the left lung. Examination of her family pedigree showed that the patient had an autosomal dominant trait of inheritance. The pathogenesis of the systemic visceral hemangiomas observed in this patient was considered to be similar to that of harmartoma.

Female↗

In vivo spectrofluorimetry reveals endogenous biomarkers that report healthspan and dietary restriction in Caenorhabditis elegans.

Autofluorescent lipofuscin and advanced glycation end-products (age pigments) accumulate with age across phyla, yet little is understood about their formation under physiological conditions and their specific contributions to the aging process. We used in vivo spectrofluorimetry to quantitate autofluorescence in wild-type Caenorhabditis elegans and longevity mutants disrupted for distinct aspects of the aging process. In wild-type animals, age pigments increase into adulthood, accumulating slowly during the reproductive phase and more rapidly during the post-reproductive period. As in humans, insulin signaling influences age pigment accumulation - mutations that lower efficacy of insulin signaling and extend lifespan [daf-2(e1370) insulin receptor and age-1(hx546) PI3-kinase] dramatically lower age pigment accumulation; conversely, elimination of the insulin-inhibited DAF-16/FOXO transcription factor causes a huge increase in age pigment accumulation, supporting that the short-lived daf-16 null mutant is truly progeric. By contrast, mutations that increase mitochondrial reactive oxygen species production do not affect age pigment accumulation, challenging assumptions about the role of oxidative stress in generating these species in vivo. Dietary restriction reduces age pigment levels significantly and is associated with a unique spectral shift that might serve as a rapidly scored reporter of the dietary restricted state. Unexpectedly, genetically identical siblings that age poorly (as judged by decrepit locomotory capacity) have dramatically higher levels of age pigments than their same-aged siblings that appear to have aged more gracefully and move youthfully. Thus, high age pigment levels indicate a physiologically aged state rather than simply marking chronological time, and age pigments are valid reporters of nematode healthspan.

Aging↗

CA19-9 may have clinical significance in mature cystic teratomas of the ovary.

The objective of this study was to evaluate size, bilaterality, histopathologic origin, and the serum levels of some tumor markers in patients with mature cystic teratomas (MCTs) of the ovary. Retrospective study of 80 patients operated at Department of Obstetrics and Gynecology, Gulhane Military Medical Academy, Turkey, between the years 1998 and 2003 was performed. The mean age was 33.1 +/- 11.3 years (median 34; range 15-69). The mean tumor diameter was 7.2 +/- 4.5 cm (median 5; range 3-20). The mean serum CA19-9 level was 101.2 +/- 179.7 IU/mL (range 1-841, normal value < 37), the mean serum CA125 level was 32.0 +/- 37.8 U/mL (range 2.2-205, normal value < 35), the mean carcino-embryogenic antigen (CEA) level was 1.46 +/- 1.20 ng/mL (range 0.2-4.8, normal value 3.4), and the mean serum alpha-fetoprotein (AFP) level was 2.7 +/- 3.0 ng/mL (range 0.1-10.5, normal value <8.1). The elevated rate of CA19-9, CA125, CEA, and AFP was 38.8% (31/80), 25% (18/72), 9.1% (4/44), and 8.7% (4/46), respectively. The bilaterality rate was 27.5% (22/80). Patients with an elevated serum CA19-9 level showed significantly higher bilaterality rate (51.6% versus 12.2%, P < 0.05) than the patients with low levels. Likelihood ratio for bilaterality was 2.8 for CA19-9 and 4.6 for CA125. Bilateral teratomas showed a significantly higher rate of ectodermal component than the unilateral ones (100% versus 74.3%, P < 0.05). Ovarian MCTs were diagnosed especially during the reproductive period. CA19-9 may be the only important marker in the diagnosis of MCTs. Elevated levels of CA19-9 and CA125 may be an indicator of bilaterality. Since levels of CA19-9 and CA125 may be elevated in both benign and malignant conditions, interpretation of these findings must be made in light of the clinical condition of the patient.

Adolescent↗

Fertility in schizophrenia: results from a contemporary US cohort.

To investigate procreation in schizophrenia, as well as gender-related differences, female patients with schizophrenia (n = 79, DSM-III-R criteria) were compared with screened female controls (n = 124) and subsequently with male patients (n = 86). Two outcomes were investigated: (i) the proportion of subjects with one or more children (an index of fertility) and (ii) the number of children per subject among those with one or more children (an index of fecundity). Multivariate analysis was used to control for confounding variables. No significant differences in fertility between female patients and controls were detected, but reduced fecundity was noted among female patients past the reproductive period. Male patients showed a significant reduction in both fertility and fecundity compared to female patients. These results suggest that there is a relatively small impairment of fecundity among female patients compared with controls, but that there are more significant gender-related differences in both fertility and fecundity. The latter have important implications for the genetics of schizophrenia.

Adolescent↗

Is irregular regression of corpora lutea in climacteric women caused by age-induced alterations in the "tissue control system"?

PROBLEM: We have recently observed that the regression of corpora lutea (CL) in women during the reproductive period of life is accompanied by a diminution of Thy-1 differentiation protein release from vascular pericytes and an accumulation of T lymphocytes and activated macrophages among both degenerating granulosa lutein cells (GLC) and theca lutein cells. These data suggest that the immune system and other stromal factors, representing components of the "tissue control system," may play a role in regression of the CL. We investigated degenerating CL from climacteric women to address the possibility that the decline of immune functions with advancing age may result in incomplete regression of luteal tissue. This could contribute to the altered hormonal profiles and abnormal uterine bleeding that frequently occur during the climacteric. METHOD: Immunoperoxidase staining and image analysis were used to localize Thy-1 differentiation protein of vascular pericytes, cytokeratin staining of GLC, neural cell adhesion molecule expression by theca lutein cells, CD15 of neutrophils, CD4, CD14, CD68, and leukocyte common antigens of macrophages, and CD3 and CD8 determinants of T lymphocytes. We also investigated the expression of luteinizing hormone receptor (LH receptor) and mitogen activated protein kinases (MAP kinases) in luteal cells. Samples of regressing luteal tissue were obtained during the follicular phase from perimenopausal women (age 45-50) who exhibited prolonged or irregular cycles. For comparison, luteal tissues from women with regular cycles (age 29-45) and CL of pregnancy were also investigated. RESULTS: Corpora lutea of the climacteric women exhibited irregular regression of luteal tissue characterized by a lack of cytoplasmic vacuolization and nuclear pyknosis in GLC, and by a persistence of theca lutein cells exhibiting hyperplasia and adjacent theca externa layers. This was accompanied by a continuing release of Thy-1 differentiation protein from vascular pericytes. Persisting GLC lacked surface expression of macrophage markers (CD4, CD14, CD68 and leukocyte common antigen) as well as nuclear granules exhibiting CD15 of neutrophils, detected in regularly regressing GLC. In addition, such persisting GLC showed weak or no LH receptor expression, and retained the expression of cytokeratin. They also exhibited enhanced staining for MAP kinases. Strong cytoplasmic MAP kinase expression with occasional nuclear translocation was also detected in persisting theca lutein cells, indicating high metabolic activity of these cells. T lymphocytes, although occasionally present in luteal stroma within luteal convolutions, did not invade among persisting GLC and were virtually absent from layers of theca externa and theca lutein cells. CONCLUSIONS: These data indicate that the regressing CL in climacteric women may exhibit persistence of luteal cells, perhaps because of age-induced alterations of the immune system and other local stromal homeostatic mechanisms involved in the elimination of luteal cells. Persisting GLC and/or theca lutein cells may exhibit abnormal hormonal secretion that contributes to the alteration of target tissues, such as the endometrium, resulting in abnormal uterine bleeding, hyperplasia, and neoplasia.

Adult↗

Focal nodular hyperplasia of the liver, benign hepatomas, oral contraceptives and other drugs affecting the liver.

Due to the claim of an association between focal nodular hyperplasia of the liver, benign hepatomas and oral contraceptives, the files in the departments of pathology at the university hospitals in Lund and Malmö were examined for these two diagnoses made since 1945 and 1957, respectively. 26 cases of focal nodular hyperplasia of the liver and 7 benign hepatomas were found, 18 and 2, respectively, in women. Since 1963, the year before oral contraceptives were introduced in Sweden, focal nodular hyperplasia has been diagnosed in 8 women in the reproductive period of life; 4 of these had taken oral contraceptives. The 4 diagnoses were established in 1972-1974. At most, 25 per cent of Swedish females between the ages of 15 and 44 years have been on oral contraceptives. The Swedish series of 28 patients with focal nodular hyperplasia comprised 3 epileptics and 3 diabetics. At least two of the epileptics had been treated with barbiturates and/or hydantoins. The prevalence of drug-treated epilepsy in Sweden is 0.4-0.5 per cent, and of diabetes about 2 per cent. The possible aetiological role of drugs provoking an increase of the smooth-surfaced endoplasmic reticulum of the liver and proliferation of vascular fibrous tissue in a part of the liver which preveiously may have been damaged by vascular disturbances or trauma, is considered. No relationship between benign hepatomas and drugs was found. The observations support the notion that oral contraceptives may be of aetiological importance in the development of focal nodular hyperplasia of the liver, although the material is too small for epidemiological and statistical analysis.

Adolescent↗

Changes in contraceptive use in Bulgaria, 1995-2000.

Comparison of results from national surveys conducted in Bulgaria in 1995 and 2000 reveal little overall change in use of modern contraceptives. Dramatic increases occurred, however, among women younger than 25 who entered their reproductive period after the end of the state socialist period. This finding suggests that contraceptive gains in the country will come largely as a cohort-replacement process. From these data, no separate program impact appears for special clinics established to provide direct, subsidized delivery of modern contraceptives to women in selected cities. The special clinics opened in cities where contraceptive use was already above the national average. During these five years, other cities lacking special clinics managed to gain in prevalence of modern contraceptive use, leaving a relatively homogenous urban-rural difference in levels of use throughout the country.

Adolescent↗

The ginkgo, the most ancient living tree. The resistance of Ginkgo biloba L. to pests accounts in part for the longevity of this species.

Fossil records clearly demonstrate that the group of trees known as Ginkgoales, of which today Ginkgo biloba is the sole living member, date back over 200 million years. Ginkgo bilboa itself is one of the oldest of living plants (4). It appears that the longevity of this tree and its long reproductive period are at least partially responsible for the persistence of the species. The resistance of these trees to pests such as insects, bacteria, viruses, and fungi has been studied. It is believed that their unusual resistance to pests accounts in part for the longevity of the trees and also, in turn, for the longevity of the species.

Air Pollution↗

Increased incidence of spontaneous abortion and infertility in women with scleroderma before disease onset: a controlled study.

A postal questionnaire was used in a nationwide case control study of women with scleroderma to investigate whether there was an increased rate of spontaneous abortion before the onset of the disease. The results from 155 case control pairs studied showed that the women with scleroderma had twice the rate of spontaneous abortion and three times the rate of fertility problems (no successful pregnancy by the age of 35) of the control women. Previous uncontrolled studies have suggested that established scleroderma is associated with an adverse reproductive history. The results from this investigation suggest that the adverse reproductive history may antedate the clinical diagnosis of scleroderma by many years and may possibly have an aetiological role. Such a hypothesis is consistent with the, as yet unexplained, marked female excess in incidence of the disease, with the peak age of onset occurring shortly after the reproductive period.

Abortion, Habitual↗

Cyclophosphamide in treatment of systemic lupus erythematosus: 7 years' experience.

This paper describes our experience with cyclophosphamide in the treatment of systemic lupus erythematosus. Since 1965 42 such patients have been treated either singly with cyclophosphamide or in combination with steroid. Serious complications have been rare except for amenorrhoea, which occurred in 14 out of 32 patients within the reproductive period. Our experience suggests that cyclophosphamide has an important, though not primary, part to play in the therapy of this disease.

Administration, Oral↗

Simple sequence repeat (SSR) markers linked to E1, E3, E4, and E7 maturity genes in soybean.

Soybean near isogenic lines (NILs), contrasting for maturity and photoperiod sensitivity loci, were genotyped with approximately 430 mapped simple sequence repeats (SSRs), also known as microsatellite markers. By analysis of allele distributions across the NILs, it was possible to confirm the map location of the Dt1 indeterminate growth locus, to refine the SSR mapping of the T tawny pubescence locus, to map E1 and E3 maturity loci with molecular markers, and to map the E4 and E7 maturity loci for the first time. Molecular markers flanking these loci are now available for marker-assisted breeding for these traits. Analysis of map locations identified a putative homologous relationship among four chromosomal regions; one in the middle of linkage group (LG) C2 carrying E1 and E7, one on LG I carrying E4, one at the top of LG C2, at which there is a reproductive period quantitative trait locus (QTL), and the fourth on LG B1. Other evidence suggests that homology also exists between the E1 + E7 region on LG C2 and a region on LG L linked to a pod maturity QTL. Homology relationships predict possible locations in the soybean genome of additional maturity loci, as well as which maturity loci may share a common evolutionary origin and similar mechanism(s) of action.

Chromosome Mapping↗

Bone changes due to pregnancy and lactation: influence of vitamin D status.

The effects of pregnancy and lactation on endosteal bone formation and resorption were evaluated in vitamin D-depleted (-D) and vitamin D-repleted (+D) rats. Pregnancy induced a marked stimulation of osteoclastic bone resorption and of static and dynamic parameters of bone formation and mineralization. Bone resorption increased independently of vitamin D status and did not correlate with plasma 1,25-dihydroxyvitamin D3 [1,25(OH)2D] levels, but it was associated with increased plasma immunoreactive parathyroid hormone (iPTH) concentrations. Stimulation of the endosteal bone formation rate was mainly impaired in D-depleted rats, resulting in trabecular bone loss, which, in -D mother rats, was associated with decreased bone ash and total bone calcium. Lactation further stimulated bone resorption and reduced the trabecular bone volume; ash weight and bone calcium content were also decreased independently of the vitamin D status and changes in plasma iPTH levels. In presence of vitamin D, the bone formation rate increased fourfold during lactation but was unchanged in -D lactating rats. During lactation, vitamin D-depleted rats lost twofold more calcified bone than +D rats because of impaired mineralization. Thus, the present study shows that both the endosteal bone resorption and formation are stimulated by pregnancy and lactation and that vitamin D is required for normal bone mineralization during the reproductive period.

Animals↗