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The ultrastructural characteristics of peri-implantation stage embryos recovered on day 6 after ovulation from rhesus monkeys with or without mifepristone (RU486) treatment during the early luteal phase were examined in the present study. Monkeys were randomly allocated to two groups; group 1 animals were injected s.c. with 2 ml vehicle (1:4, benzyl benzoate: olive oil, v/v, n = 21) and group 2 animals received a single dose of mifepristone (2 mg/kg body weight, w/v, n = 30) in the same volume of vehicle on day 2 after ovulation in mated cycles. On day 6 after ovulation, female monkeys of both groups were laparotomized and their reproductive tracts were flushed to retrieve preimplantation stage embryos. Embryos that showed frank degeneration or desynchrony on gross microscopical examination were not included in the present study. Preimplantation embryo growth on day 6 after ovulation was significantly (P < 0.05) affected in the morula-blastocyst transition stage in mifepristone-treated monkeys compared with that in the control group of monkeys. Ultrastructurally, administration of mifepristone on day 2 after ovulation depressed preimplantation stage embryo development, characterized by loss of cell polarity, lack of mitochondrial maturity, and lack of differentiation in trophoblast cells. Furthermore, preimplantation embryos from mifepristone-treated animals displayed a higher occurrence of inter-blastomere space, intra-cytoplasmic vacuoles, myelinoid bodies, accumulation of lipid droplets, lysosomes, lipofuscins, autophagosomes and multivesicular bodies. Collectively, it appears that the developmental potential of preimplantation embryos was significantly compromised in mifepristone-treated cycles. [ABSTRACT FROM AUTHOR]

The aim of the present study was to examine the cellular basis of the involvement of oestradiol and progesterone in blastocyst implantation in the primate. To this end, the cellular distribution of receptors for oestradiol (ER) and progesterone (PR) in fetal trophoblast cells and in endometrial compartments of timed lacunar (pre-villous) and villous stages of placentation in primary implantation sites collected on days 13-22 of gestation were investigated in rhesus monkeys. Both in pre-villous stage tissue and in villous stage tissue, cytotrophoblast cells and syncytiotrophoblast cells and other trophoblast derived cells were PR positive, while they were generally ER negative. Maternal endometrial cells were ER negative, while epithelial cells, stromal cells and vascular endothelial cells in maternal endometrium showed heterogeneous staining patterns for PR depending on their relative location; these patterns, however, correlated well with glandular hyperplasia and differentiation, stromal-decidual transformation and vascular response seen during blastocyst implantation. [ABSTRACT FROM AUTHOR]

Epithelial cells were isolated from normal human endometrium and cultured on reconstituted matrices of rat-tail collagen gels. Cells attached within 24 h after plating. Initially, epithelial cells were not structurally polarized, had projections from both apical and basal domains and were generally flat to cuboidal in shape. When the gels were made free floating 36-48 h after initiation of the cultures, the epithelial cells became columnar in shape as the gels underwent contraction. Although a maintained growth profile was observed during the 10 days of culture, there was a linear decrease in gel matrix diameter along with increasing loss of transparency. Electron microscopy revealed the presence of apical microvilli, junctional complexes, lipid droplets and endoplasmic reticulum in cultured epithelial cells. The basolateral dilatations and lateral membrane plications were seen in these cells by 6-8 days in culture. With gel contraction, rearrangement of matrix material was observed. Occasionally there were basal lamina-like structures adjacent to the flattened basal surface and the formation of gland-like structures within the matrix. The three-dimensional primary culture of human epithelial cells on collagenous biomatrix appears to be a potential experimental tool for the study of cell-cell and cell-matrix interactions, and of the study of the effects of endocrine and paracrine factors on these cells in vitro. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate whether luteal phase ovarian oestrogen is required for blastocyst implantation and pregnancy maintenance in the rhesus monkey. Preimplantation embryos were retrieved from naturally ovulated, mated embryo donor monkeys. In group I, developmentally normal, age- and stage-matched embryos were transferred to recipient monkeys showing naturally synchronized ovulatory cycles. Immediately prior to embryo transfer, recipients were subjected to bilateral ovariectomy, and following transfer they were treated with i.m. injections of either progesterone (group Ia, n= 4), or oestradiol + progesterone (group Ib, n= 2). Recipient monkeys of group Ic (n= 4) were subjected to sham ovariectomy and vehicle injection. In group Ia, progesterone supplementation alone led to three pregnancies and live births. In group Ib, there was one live birth. In the control group Ic, four transfers resulted in two live births and one abortion on cycle day 58. Analysis of serum progesterone and oestradiol profiles showed that oestradiol had declined to undetectable levels within 3–5 days after ovariectomy in group Ia recipients, and the area under the curve of serum oestrogen concentrations during the peri-implantation period (days 10–20 after ovulation) were less (p< 0.001) in group Ia compared with group Ic. There were no changes in the area under the curve among serum progesterone concentrations in all the subgroups. In group II, long-term ovariectomized embryo recipients (n= 4) were primed with oestradiol till cycle day 11 of simulated transfer cycle, and received progesterone treatment from cycle day 10 till the end of the experiment. Of four transfers, live births were recorded in two cases, while in one case abortion occurred on cycle day 66. Serum oestradiol concentrations were undetectable during the presumptive peri-implantation period of pregnancy cycles in group II recipient monkeys. Noyes‘ dating of endometrial samples collected from both groups on days 5–7 after the oestrogen rise revealed that endometrial histology synchronized well with those found during days 3–5 after ovulation in normal menstrual cycle. We conclude that luteal phase ovarian oestrogen is not essential for progesterone-dependent endometrial receptivity and response leading to implantation and pregnancy maintenance in the rhesus monkey. [ABSTRACT FROM PUBLISHER]

The morphological characteristics of endometrium on day 6 after ovulation of conception (group 1) and non-fecund, menstrual (group 2) cycles have been studied in the rhesus monkey (n = 30). A conception cycle was distinguished by the presence of a developmentally normal, age-stage-synchronized embryo. Thus, 78% of the mated cycles (n = 18) yielding synchronous embryos (12 zona-encased and two zona-free blastocysts) were used for this study. On day 6 after ovulation, no significant changes in the serum concentrations of oestrogen and progesterone were seen in conception cycles (n = 14) compared with the non-mated, normal ovulatory cycles (n = 12). Morphometric analyses revealed that on day 6 of gestation (n = 8), endometrium differed from the corresponding non-mated luteal phase (n = 7) with significant increases in epithelial mitosis (P < 0.01), height of glandular epithelium (P < 0.05), volume ratio of gland cell to gland (P < 0.03), degree of pseudostratification (P < 0.02), and higher frequency of supranuclear, adluminal accumulation of vacuoles in gland cells (P < 0.05). The degree of stromal oedema was higher (P < 0.02) in fecund cycles but there was no change in venular diameter. In a separate set of experiments, estimates of tissue vascular response revealed a higher (P < 0.02) endometrial extravascular albumin space on the same day of gestation; there were no differences, however, in endometrial blood volume, or in the number of von Willebrand antigen-positive capillaries and small vessels between the two groups (group 1, n = 6; group 2, n = 5).(ABSTRACT TRUNCATED AT 250 WORDS) [ABSTRACT FROM AUTHOR]

The hypothesis that post-coital administration of mifepristone (RU 486) as a single dose in the early luteal phase can be an effective anti-nidatory strategy was tested using the rhesus monkey as the experimental model. Incidence of pregnancy, vaginal bleeding patterns, profiles of menstrual cyclicity and of serum levels of progesterone and oestrogen were examined following administration of RU 486 as a single dose of 10 mg/kg and 2 mg/kg body weight on the second day after ovulation. In control monkeys (group 1; = 5) receiving the vehicle alone (benzyl benzoate: olive oil, 1: 4, v/v) there was a 60% pregnancy rate. Following s.c. administration of RU 486 at both doses, no pregnancy was recorded in a total of 33 treatment cycles in 12 monkeys. Five monkeys received RU 486 at 10 mg/kg s.c. (group 2) in three consecutive cycles. All animals had complete inhibition of implantation; in addition, the treatment cycle length was prolonged ( < 0.001) due to an extension of the luteal phase. The subsequent follicular phase was unaffected. Mild, premature vaginal bleeding during the luteal phase was recorded in five treatment cycles, 3–5 days after drug application. Though the serum profiles of progesterone and oestrogen in these monkeys showed marked individual variations, there was a characteristic progesterone rebound about 18–20 days after drug administration. Monkeys in group 3 were given RU 486 at 2 mg/kg, s.c. either for three consecutive cycles (group 3a; = 4) or for two consecutive cycles (group 3b; = 3). Premature luteal phase vaginal bleeding occurred only in four treatment cycles, within 2–6 days post-treatment. An increase in both the duration ( < 0.001) and degree ( < 0.001) of menstrual flow as compared with the pre-treatment cycles was recorded in six treatment cycles of three monkeys in group 3. These animals did not have premature luteal phase vaginal bleeding. Collectively, 100% protection against pregnancy with no change in the cycle length was obtained in all seven monkeys in 18 treatment cycles. Analysis of pooled data revealed that the subsequent follicular phase, as well as the ovarian steroid hormone profiles of treatment cycles were unaffected. Thus, a single application of RU 486 in the early secretory phase appears to be a potential anti-implantation strategy for intercepting pregnancy in the primate. [ABSTRACT FROM PUBLISHER]

Using the artificial plaque--decidual cell model in rhesus monkeys, the potential role of progesterone in the process of of epithelial and stromal cell responses was investigated by time-adjusted application of an antiprogestin, RU 486. Epithelial plaque formation is an immediate response of the endometrium to either trauma or invading trophoblast cells. To study this process, RU 486 (2.5 mg/kg body weight) or vehicle (ethanol/saline, 7:3, v/v, i.m.) was administered to the first group of monkeys immediately following traumatization (days 16 and 17 of treatment cycle). Histometric analysis revealed that treatment with RU 486 led to significant inhibition (P less than 0.001) in the recruitment of epithelial cells into plaque acini and consequent reduction (P less than 0.001) in the spread of the plaque reaction compared with control monkeys. In the second group of monkeys, experimental treatment was delayed until plaque formation had occurred (days 21 and 22 of cycle). RU 486 induced increased degeneration (P less than 0.01) in plaque cells. Thus the transformation and the maintenance of the epithelial plaque response appears to be progesterone-dependent. Glandular epithelium showed only marginal changes (P less than 0.05) in maximum cell height, amount of pseudostratification and secretory activity of glands as a consequence of RU 486 treatment; however, the antiprogestin induced a higher incidence of glandular apoptosis (P less than 0.01 for both groups). It has been suggested that the higher degree of apoptosis in the glandular epithelium could be a consequence of the progesterone receptor blocking action of RU 486. No distinctive change in endothelial cell ultrastructure was evident following RU 486 treatment; however, venular diameter was significantly increased (P less than 0.01, group I; P less than 0.001, group II) along with an apparent reduction in the extent of oedema. There was increased extravasation (P less than 0.01) and leukocytic infiltration (P less than 0.001, group I; P less than 0.05, group II) following RU 486 treatment. RU 486 induced vascular responses and increased diapedesis could presumably have resulted from its progesterone blocking action in vascular cells. RU 486 accelerated the incidence (P less than 0.01) of stromal decidualization (group I), as well as quantitatively accentuating (P less than 0.001) the decidual cell reaction (group II). It is possible that RU 486 may inhibit specific functions of decidual cells, despite morphologically consistent decidual transformation. [ABSTRACT FROM AUTHOR]

It is becoming increasingly evident that growth factors and cytokines play crucial roles in the process of blastocyst implantation. Endometrial differentiation and secretions, embryo development and secretions, and embryo-endometrium interaction leading to implantation require continuous and synchronous dialogue between these two compartments involving endocrine and paracrine regulators. In this review, a model of the endocrinology and paracrinology of blastocyst implantation in the primate is described. [ABSTRACT FROM AUTHOR]

The characteristics of implantation stage endometrium following a single-dose, early luteal phase application of mifepristone (RU486) in proven conception cycles has been examined in the rhesus monkey in an attempt to understand the physiological basis of the anti-implantation activity of the drug. Endometrial samples were collected from monkeys subjected to vehicle (group 1, n = 14) and RU486 (2 mg/kg body weight; group 2, n = 12) on day 2 after the presumed day of ovulation of successfully mated cycles. The average diameter of glands (P < 0.05), number of vacuolated cells (P < 0.01), number of supranuclear vacuolated cells (P < 0.05) in glandular epithelium and amount of glandular secretion (P < 0.05) were significantly lower in RU486-treated endometrium compared with control tissue samples. Additionally, 18% of glandular epithelial cells showed apoptotic and degenerative features in RU486-treated tissue samples. These data, together with the observed significant decreases in precipitate area (P < 0.02) and in the optical absorbance of alkaline phosphatase reaction end-product (P < 0.05), confirm that retardation in glandular differentiation in the upper functionalis is a likely target of antiprogestin action in implantation stage endometrium. An increased frequency of mitosis in stromal cells (P < 0.05) and a greater degree of extravasation (P < 0.05) were also observed after RU486 exposure. Despite an apparent indication of constriction and regression in few RU486-exposed endometria compared with controls, morphometric analyses did not show any changes in capillary structure. Whether endometrial vasculature in progesterone-exposed uterus is a target of antiprogestin action during the peri-implantation stage remains to be determined. Further studies are required to explain the observed increase (P < 0.02) in the area of precipitate of von Willebrand (vW) factor with no change in vW factor-positive vessels, and the apparent increase in collagen IV immunostain in subepithelial and perivascular basement membrane in implantation stage endometrium after early luteal phase RU486 treatment in monkeys. [ABSTRACT FROM AUTHOR]

Investigates the stability characteristics of an optimal economic control policy with a quadratic performance integral and a linear macro-dynamic model. Details of mathematical models based on the multiplier and acceleration principles; Discussion on the problem of specification of stabilization policies on the Hicksian nonlinear trade cycle model. [ABSTRACT FROM AUTHOR]

The implications of a fractile approach to linear programming under risk through maximizing a given fractile of the distribution of profits under linear programming restrictions are examined here both theoretically, computationally and empirically. [ABSTRACT FROM AUTHOR]

A linear programming problem is said to be stochastic if one or more of the coefficients in the objective function or the system of constraints or resource availabilities is known only by its probability distribution. Various approaches are available in this case, which may be classified into three broad types: 'chance constrained programming', 'two-stage programming under uncertainty' and 'stochastic linear programming'. For problems of 'stochastic linear programming' a distinction is usually made between two related approaches to stochastic programming, the passive and the active approach respectively. In the passive approach to stochastic linear programming the statistical distribution of the optimum value of the objective function is estimated either exactly or approximately by numerical methods and optimum decision rules are based on the different characteristics of the estimated distribution. In the active approach, a new set of decision variables are introduced which indicate the proportions of different resources to be allocated to the various activities. One effect of introducing this set of new decision variables in the active approach is the truncation of the statistical distribution of optimal value of the objective function of the passive approach. In this aspect the active approach is useful in suggesting criteria for changing from one optimum decision rule to another, as the probability distribution of the objective function is specified less and less incompletely for different choices of the set of new decision variables. This paper investigates some mathematical relations between the active and passive approach and derives some inequalities for the case when the elements of the coefficient matrix of the inequalities are random variables. Since an 'approximate solution' of a stochastic linear programming problem is defined usually by replacing each random element by its expected value and then solving the resulting non-stochastic program, some conditions have been derived under which the expected value of the objective function for the optimal solution will exceed the optimal value of the objective function for 'the approximate solution'. Based on the properties of the distribution of extreme values and other order statistics, some approximate bounds have also been specified for the passive approach, which can easily be extended to the active approach. [ABSTRACT FROM AUTHOR]

The approach of chance-constrained linear programming is analyzed here in the context of safety-first principles based on Tchebycheff-type inequalities. The analysis attempts to define relatively distribution-free tolerance levels and the incidence of nonnormality in chance-constrained linear programming. [ABSTRACT FROM AUTHOR]

Studies were carried out on 879 healthy soldiers of ages ranging from 18-46 years to assess the effect of age, if any, on physical work capacity. These subjects were in a fairly controlled state of nutrition and physical training. A battery of tests was administered under outdoor conditions as well as in the laboratory. It was found that all the physical functions tested, such as speed of running, abdominal muscle strength, agility, arm and shoulder muscle strength and capacity for short bursts of activity, started to show deterioration after 30 years, and the process was progressive thereafter. Judged from these performances the subjects seemed to fall into three distinct age groups, viz. 18-30, 31-37 and 38–43. The subjects above 43 years were too few to be considered for analysis. The mean maximum oxygen consumption was found to be 47.7 ml/kg/min in the 18-30 years group, and it was reduced to 45.8 and 42.1 ml/kg/min for the two higher age groups respectively. Excess lactic acid build-up due to a standard stepping exercise was also found to increase with age, and the tolerance time in endurance tasks was found to reduce with increasing age. Performance in the running test correlated highly with the values for maximum oxygen consumption and endurance stopping, thereby indicating that even simple outdoor tests like running can be effectively used for assessing the physical work capacity, especially under field conditions. [ABSTRACT FROM PUBLISHER]

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The article presents the abstracts of several papers on economics published in the October 1965 issue of the journal "Zeitschrift Für Die Gesamte Staatswissenschaft." The first paper of the journal "The Problem of Middle Europe, 1840-1940," by W.O. Henderson, discusses the possibility of extending German economic and political influence in central Europe. The second paper of the journal is "General Economic Theory and Spatial Economic Relations," by E.V. Böventer. Confronting the terms general economic theory and spatial economic relations the author examines the tools that have been developed for the analysis of a spaceless economy in the light of their capability to analyze problems of a space-economy. The third paper "Optimum Economic Policy for Stabilization With a Quadratic Criterion Function," by J.K. Sengupta, analyzes the nature and implications of instability generated by the so-called shock variables. The question of an appropriate stabilization policy emphasizing the two-fold objectives of stability and optimality is also discussed in relation to the Hicksian non-linear trade cycle model extended to include government expenditure as an additional variable.

This article presents abstracts of several papers about economics published in the November 1964 issue of the journal Oxford Economic Papers. In the article Static Multipliers and Social Accounting Systems, F. Seton developed a matrix notation to show the social accounting effects of monetary transactions and illustrated the resulting causal chains. While the article Structural Inflation and Latin American Structuralism, dealt with the so-called structuralist doctrine of inflation, sustained by many Latin American economists.

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