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The effect of ethanol upon early development in mice and rats. I. In vivo effect upon preimplantation and early postimplantation stages.

The preimplantation and early postimplantation effect of chronic alcohol consumption (at least a month before mating and during pregnancy until killing) and of acute ethanol intoxication during the preimplantation period (i.v. infection of ethanol) was studied on albino rats (Wistar) and albino mice (RAP). The main results were as follows: Chronic alcoholization. Rats: significant retardation of preimplantation development and in early postimplantation stages; a tendency of lowering of the mean litter size. Mice: significant increase of the number of preimplantation pathological forms; a tendency of lowering of the mean litter size. Pathological changes show, both in rats and mice, an obvious "litter effect". Acute ethanol intoxication. Rats: significant retardation in some litters, normal or even advanced development in others. This effect differs from the previously reported effect of acute ethanol intoxication during early postimplantation stages. The results obtained attest the prenatal noxious effect of chronic ethanol consumption in both species used and of acute ethanol intoxication during preimplantation development upon early postimplantation development in rats. Within the limits of extrapolation possibilities, they represent a risk signal for other species (including human).

Alcoholic Intoxication↗

Renal ostodystrophy during the developing stage of maintenance dialysis in Transylvania. Early development of periarticular calcifications and beta 2 microglobulin amyloidosis in spite of a relatively good prevention of secondary hyperparathyroidism.

BACKGROUND: Dialysis facilities have been introduced only recently in Transylvania with many limitations, in particular a standard high calcium dialysate, Al(OH)3 as phosphate binder and pharmacological doses of native vitamin D2, but neither CaCO3 nor 1 alpha hydroxylated vitamin D. Rheumatological complaints and metastatic calcifications were frequent, leading to suspect either overt hyperparathyroidism, adynamic bone disease or beta 2 microglobulin amyloidosis. AIMS OF THE STUDY: Evaluate the prevalence of radiological osteitis fibrosa, amyloid osteoarthropathy and periarticular calcification and their link with PTH secretion, phophocalcic disorders, acidosis, bone turn over, aluminum and beta 2 microglobulin accumulation in the dialysis population of Sibiu (Transylvania). METHODS: The clinical and radiological rheumatological data of the 49 uremic patients dialyzed in Sibiu since 1990 were reviewed as well as the monthly routine monitoring of their plasma phosphocalcic parameters. Furthermore in July 1994, 36 of them had an X rays of the hands for evaluation of subperiosteal resorption of the phalanges, periarticular calcifications and carpal cysts as well as a determination of plasma concentrations of intact PTH (normal range: 10-55; optimal range: 100-200 pg/ml), osteocalcin, bone alkaline phosphatase, aluminum and 25 OH vitamin D. RESULTS: The prevalence of subperiostal resorption of the phalanges was 8% and that of severe biological hyperparathyroidism (PTH > 400 pg/ml) 22%, whereas that of a relative hypoparathyroidism (PTH < 100 pg/ml) was 31%. Mean plasma concentrations of calcium was 2.07 +/- 0.15; of phosphate 2.50 +/- 0.35; of bicarbonate 15 +/- 2.0 mmol/l, of 25 OHD 30 +/- 20 ng/ml, of aluminum 1.1 +/- 0.5 mumol/l. Plasma PTH concentrations were negatively correlated to dialysis duration, and to plasma concentrations of aluminum, calcium and 25 OH vitamin D but not to those of phosphate and bicarbonate. Multivariate analysis showed however that only duration of dialysis and plasma aluminum concentration were independently and negatively correlated to plasma PTH concentrations. The prevalence of periarticular calcifications (26%) and of carpal cysts suggestive of beta 2 microglobulin amyloidosis (10%) were relatively high considering the young age of the population (42 years) and the short duration of dialysis (2.6 years). Patients with calcifications comparatively to those without calcifications were older, had longer duration on dialysis, higher prevalence of carpal cysts and higher plasma beta 2 microglobulin concentrations, lower plasma PTH (98 versus 313 pg/ml) and higher plasma aluminum concentration (1.3 versus 0.8 mumol/l). Patients with carpal cysts comparatively to those without cyst were older, had a longer duration on dialysis and a higher prevalence of periarticular calcifications. CONCLUSIONS: a) In spite of no use of 1 alpha hydroxylated vitamin D derivatives, and poor control of hyperphosphatemia and acidosis, hyperparathyroidism declined with duration of dialysis due to the use of a high dialysate calcium concentration, Al(OH)3 as sole phosphate binder and high supplement of native vitamin D. b) Considering the relative young age and short duration on dialysis, the prevalence of periarticular calcifications and carpal cysts were high. c) Calcifications were possibly favored by relative hypoparathyroidism and moderate aluminum overload. d) The association of periarticular calcifications and subchondrial cysts suggest a causal relationship.

Adult↗

The system specifying body position in the early development of Xenopus, and its response to early perturbations.

Evidence is presented that the system setting up preliminary specifications for contributions to the axial body plan, across vegetal regions of the Xenopus embryo, acts in a widespread way at early stages. Mechanisms that regulate the spatial profile of this primary positional variable, and thus ensure the constancy and harmony of the body plans normally achieved, have lost this integrative ability by the 4-cell stage one hour after the plasm shifts that precede first cleavage and symmetrize the egg. Abnormal, partial or distorted profiles of the positional system across whole eggs or isolates, recorded by these times, are retained to give correspondingly partial or imbalanced mes/endodermal pattern at tailbud larval stages. There is evidence that subsequent 'back-up' positional interactions, which can heal gross positional discontinuities in isolated presumptive lateral half-eggs and so restore bilateral symmetry, also do this at the price of loss of complete pattern specification. This is probably because of an asymmetrical principle whereby relatively activated (dorsoanterior specified) material can raise the level of originally posterior material on contact, whereas the reverse interaction cannot occur. The observations are discussed in relation to apparently different behaviour in certain other amphibian embryos, and to our knowledge of other positional interactions, normal and also experimentally provoked, such as those that set up the germ layers.

Animals↗

Predictors of the early development of advanced metachronous colon adenomas.

BACKGROUND/AIMS: In order to reduce the number of colonoscopies performed for the surveillance of patients after polypectomy, suitable predictors of adenomas recurrence are needed. The aim of this study was to find predictors of the early development of metachronous adenomas and specifically of advanced ones. MATERIALS AND METHODS: Forty-four patients underwent total colonoscopy 24-26 months after initial endoscopic polypectomy. All polyps were endoscopically removed and an adenoma was considered as advanced if the diameter was > 1 cm and/or villous component and/or severe dysplasia were present. RESULTS: Metachronous adenomas were detected in 16 (36.4% patients. Five (11.4%) of them had advanced metachronous adenomas. Early recurrence of adenomas was significantly correlated with the total number of indices adenomas (p = 0.027). On the contrary, the presence of metachronous adenomas was not related to any of the patients' characteristics nor to the site and the histology of the indices adenomas. The development of advanced metachronous adenomas during the same period was significantly correlated with patients' age, as it was observed only in patients aged > or = 60 years (5/21 or 23.8%) and in none of the patients aged < 60 years (Odds ratio: 15.7, p = 0.02). Logistic regression analysis revealed that patient's age was the only significant predictor of the early development of advanced metachronous adenomas (beta = 0.40, p = 0.02) and that the number of the indices adenomas was the only significant predictor for the recurrence of all adenomas (beta = 1.59, p = 0.02). CONCLUSIONS: 1. Only patients aged > or = 60 years seem to develop advanced metachronous adenomas two years after polypectomy and 2. The likelihood for developing metachronous adenomas during the same period is related to the number of indices adenomas.

Adenoma↗

DNA methyltransferase is actively retained in the cytoplasm during early development.

The overall DNA methylation level sharply decreases from the zygote to the blastocyst stage despite the presence of high levels of DNA methyltransferase (Dnmt1). Surprisingly, the enzyme is localized in the cytoplasm of early embryos despite the presence of several functional nuclear localization signals. We mapped a region in the NH(2)-terminal, regulatory domain of Dnmt1 that is necessary and sufficient for cytoplasmic retention during early development. Altogether, our results suggest that Dnmt1 is actively retained in the cytoplasm, which prevents binding to its DNA substrate in the nucleus and thereby contributes to the erasure of gamete-specific epigenetic information during early mammalian development.

Alternative Splicing↗

Transcriptional regulation of tubulin gene expression in differentiating trochoblasts during early development of Patella vulgata.

The expression of alpha- and beta-tubulin genes during the early development of the marine mollusk Patella vulgata has been investigated. From the 32-cell stage onwards, an enhanced expression of both alpha- and beta-tubulin mRNAs was detected in the primary trochoblasts. After one additional cleavage, these cells become cleavage-arrested and then form cilia. They are the first cells to differentiate during Patella development. Later, alpha- and beta-tubulin mRNA is also found in the accessory and secondary trochoblasts. Together these three cell-lines form the prototroch, the ciliated locomotory organ of the trochophore larva. The early and abundant expression of tubulin genes precede and accompany cilia formation in the trochoblasts and provides us with an excellent molecular differentiation marker for these cells. Apart from the trochoblasts, tubulin gene expression was also found in other cells at some stages. At the 88-cell stage, elevated tubulin mRNA levels were found around the large nucleus of the mesodermal stem cell 4d. In later stages, tubulin gene expression was detected in the cells that form the flagella of the apical tuft and in the refractive bodies. An alpha-tubulin gene was isolated and characterized. A lacZ fusion gene under control of the 5' upstream region of this tubulin gene was microinjected into embryos at the two-cell stage. The reporter gene product was only detected in the three trochoblast cell-lines at the same time as tubulin genes were expressed in these cells. Reporter gene product was not detected in any other cells. Thus, this 5' upstream region of this alpha-tubulin gene contains all the elements required for the correct spatiotemporal pattern of expression.

Amino Acid Sequence↗

Early development of the tush and the tusk of the African elephant (Loxodonta africana).

This early development was studied from a serial histological sections of eight elephant embryos with masses varying between 1 and 240 g. The tush and the tusk develop from one tooth germ in a deciduous to permanent tooth relation. In order to study the mineralization of the dental organ of the tush and cap and bell stage of the tusk, embryos older than 3-months' gestation (weighing more than 250 g) would be required.

Animals↗

The early development and ossification of the human clavicle--an embryologic study.

Morphologic studies of the early development of the clavicle were carried out in 46 human embryos and fetuses ranging in age from 6 to 12 weeks. We confirmed that the clavicle is formed by two membranous primary ossification centers appearing by 6 weeks and fusing approximately 1 week later. Cartilage at both ends of the clavicle then develops. In time, the medial cartilaginous mass contributes more to the growth in length of the clavicle than the lateral cartilaginous mass. The spatial orientation of both ossification centers and the development of enchondral bone formation at the ends of the clavicle lead to its characteristic shape. Interestingly, the primary ossification centers contribute little to the growth in length. The junction of the two centers of ossification is situated between the lateral and middle third of the clavicle and, consequently, does not correspond to the site of congenital pseudarthrosis, which is located in the middle part of the clavicle.

Clavicle↗

Circadian adrenocortical periodicity changes in adult rats stimulated during early development--II. Effect of cold stress.

Rats were cooled at different time points of early postnatal development to study the effects of short-term stress on the parameters of the circadian rhythm of the adrenocortical function in adults. It was found that rats stressed at the age of 2-4 or 17-19 days exhibit modified timing in the circadian periodicity of the adrenocortical function as adults. Cold stimulation during early development does not affect the function of isolated adrenal glands in vitro. It is concluded that the effect of early stress on the adrenocortical rhythmicity in adults is mediated through central regulatory mechanisms. This effect depends on the age when the rat pups are exposed to cold stress.

Adrenal Cortex Hormones↗

Low temperatures during early development influence subsequent maternal and reproductive function in adult female mice.

Challenging conditions early in development can have enduring effects into adulthood. The effects of low temperatures were examined on subsequent sex-specific morphology (anogenital distance [AGD]), maternal care, and reproductive performance in adult female mice. Dams (F0) were maintained either in (1) standard laboratory room temperatures (21 +/- 2 degrees C) or (2) low temperatures (10 +/- 2 degrees C) throughout gestation. Their progeny (F1) either remained in the temperature condition in which they were conceived or were switched to the other temperature condition at 2 days of age until weaning. Reproductive performance and maternal behaviors were assessed in adulthood. F0 dams that were maintained in low temperatures bore larger litters as compared to F0 animals housed in standard temperatures throughout their pregnancy. In contrast, mean litter size was reduced for all groups of F1 females that experienced low temperatures. Infant mortality was elevated in litters of F1 females that were exposed to low temperatures both before and after birth. Prenatal exposure to low temperatures was associated with reduced responsiveness towards the nursing young and decreased maternal aggression in F1 animals. Prenatally treated F1 females had longer, male-like AGDs on Day 2 following birth compared to animals not subjected to experimental manipulations. Our results indicate that exposure to low temperatures during early development impairs reproductive function and is associated with important fitness costs as evidenced by reduced offspring survival. Our findings also suggest that chronic low temperatures experienced only after birth may have less deleterious effects than exposure to a combination of pre- and postnatal or prenatal treatments alone.

Aggression↗

The emergence and early development of autobiographical memory.

The authors provide a new framework that integrates autobiographical memory with other early achievements (e.g., gesturing, language, concept formation). In this theory, the emergence and early development of autobiographical memory does not require the invocation of specialized neurological or multiple memory mechanisms but rather arises as a natural consequence of developments in related domains including in the "software" that drives general memory functioning. In particular, autobiographical memory emerges contemporaneously with the cognitive self, a knowledge structure whose features serve to organize memories of experiences that happened to "me." Because this cognitive self emerges in the 2nd year of life, the lower limit for early autobiographical memories is set at about 2 years, with subsequent accumulation of memories linked to improvements in children's ability to maintain information in storage.

Autobiographies as Topic↗

AstroNewt: early development of newt in space.

AstroNewt experiment explores the effects of earth gravity on the early development of Japanese red-bellied newt, Cynops pyrrhogaster. Since female newts keep spermatophore in cloaca, fertilized eggs could be obtained without mating. Fertilization of newt's egg occurs just prior to spawning, so that gonadotrophic cues applied to females in orbit leads to laying eggs fertilized just in space. A property of newt being kept in hibernation at low temperature may be of great help for the space experiment carried out with much limited resources. A general outline of the AstroNewt project is shown here in addition to some technical advances for the development of the project. Experimental schemes of two space experiments (IML-2 in summer 1994 and unmanned SFU at the beginning of 1995) are also shown.

Animals↗

Matrix constituents of early developing bone examined by freeze fracture.

Specimens of aldehyde-fixed and glycerol-impregnated early developing bone matrix, obtained from rat calvaria, were examined by the freeze-fracture method. The developing bone matrix reveals collagen fibrils, numerous membranous structures and a granular background. The collagen fibrils, when viewed longitudinally, exhibit a substructure of thinner filaments (microfibrils) which appear to follow a twisted course along the fibril-axis. Some of the membranous structures are readily identified as osteoblast processes. Others, which are round, ovoid or irregular in shape, were found either with or without intramembrane particles (IMPs). It is concluded that the round or ovoid IMP-containing membranous structures correspond to matrix-vesicles. The nature of the IMP-free bodies, however, is uncertain. They may be artefacts or genuine matrix-vesicles deriving from unstable membrane domains which have a propensity for blebbing or budding off. Confirmation of the latter possibility might come from examination of directly frozen specimens.

Animals↗

Cell division-associated expression of an epitope, KH17, on early developing thymocytes.

A newly established monoclonal antibody, KH17, detects a unique epitope temporarily expressed on early developing CD3-thymocytes confined to a cycling stage. KH17 is detectable on a part of CD4-CD8-,CD4-CD8+, and CD4+CD8+ cells, but not on CD4+CD8- thymocytes. By four-color flow cytometry analysis using KH17, we were able to define the heterogeneity of immature CD4-CD8- thymocytes by the expression of KH17 and IL-2R. In Thy-1-congeneic bone marrow chimeras, the appearance of KH17-IL-2R+ thymocytes preceded the increase of KH17+IL-2R- cells. The antibody could also divide CD3-CD4-CD8+ cells into two subpopulations, KH17+ and KH17-, which showed a continuum. In the fetal thymus there was a rapid and dramatic increase of KH17-CD4+CD8+ thymocytes concomitant with a decrease of KH17+CD4-CD8+ thymocytes in later gestation days. KH17 is not expressed on resting peripheral T cells, but is expressed on a large proportion of Con A-activated blastic spleen cells. The KH17 molecules precipitated from Con A-activated spleen cells were 55 and 75 kd polypeptides, but different from IL-2R subunits.

Animals↗

Aspartate aminotransferase activity during early development of chicken embryo.

Aspartate aminotransferase (AAT) activity is studied, employing two different procedures, during early development stages of chicken embryo. ATT activity is steady from pre-streak to the definitive primitive streak stage after which it suddenly increases as growth proceeds. INH or IIH administration in this embryonic system led to almost instantaneous and complete disappearance of AAT activity which could be reversed to 80 percent by treatment with equimolar pyridoxal phosphate. Histochemical studies from the literature support a view that the period of intense differentiation coincides with an increased RNA content. The present study shows more AAT activity per mg wet embryo during the same development stages. Whether this is due to availability of more aspartic acid for pyrimidine is not clear due to possible presence of two AAT activities, the many competing reactions that can use aspartic acid, and in situ conditions during differentiation.

Animals↗

Invasion and early development of Sarcocystis muris (Apicomplexa, Sarcocystidae) in tissue cultures.

Ultrastructural observations on the invasion and early development of merozoites (bradyzoites) of Sarcocystis muris in Madin-Darby canine kidney (MDCK) cells are presented. Invading merozoites cause the host cell plasmalemma to invaginate; they form a membrane junction (moving junction) and move into the host cell where they are enclosed in a primary parasitophorous vacuole (PV). Within 30-45 min after becoming intracellular, merozoites begin to vacate the newly established primary PV and move, forming a new membrane junction, into a secondary PV. Simultaneously with the movement of the parasite, the contents of dense granules in the apical part of the merozoites are shed by exocytosis into the lumen of the developing secondary PV. A lamella of the endoplasmic reticulum of the host cell becomes attached to the PV membrane, forming a PV limited by three host cell membranes.

Animals↗