Development of the notochord in normal and malformed human embryos and fetuses.

In view of its possible involvement in early embryogenesis and teratogenesis, the developmental characteristics of the human notochord were studied by light and electron microscopy and immunohistochemistry on 20 human conceptuses (5th-22nd week). At the earliest embryonic stages examined, the notochord is closely related to both the pharyngeal endoderm and the neuroectoderm of the posterior (tail) end of the neural tube. In both regions the interspace is bridged by slender cytoplasmic processes, lined with basal lamina and filled with amorphous extracellular material containing collagen types III and IV and laminin. The notochordal cells express cytokeratin brightly and vimentin weakly. As embryonic age progresses, the notochord gradually separates from the epithelia, becomes the axis of developing spinal column and undergoes progressive cell degeneration and rearrangement within the vertebral bodies. This is associated with extensive production of extracellular material and the first appearance of fibronectin. Intracellularly, the expression of vimentin gradually increases, while that of cytokeratin slightly weakens. Changes in the notochord parallel other developmental events in axial organs. In anencephalic fetuses the course of the notochord is irregular and partly interrupted with segments outside the basichondrocranium in specimens with craniorachischisis.     

The menopause,hormone replacement therapy and breast cancer

Concern exists that the reduction in breast cancer risk associated with the onset of the menopause will be negated with exposure to hormone replacement therapy (HRT). Evidence from large-scale randomised HRT trials support observational data that have shown a modest increase in breast cancer risk with long-term use (i.e. >15 years) of combined therapy, although this falls following HRT cessation suggesting a growth-promoting effect. Randomised evidence demonstrates that the efficacy of anti-estrogens, aromatase inhibitors and raloxifene in the treatment and chemoprevention of breast cancer are restricted to women with oestrogen receptor positive (ER +ve) disease; however, HRT has not been associated conclusively with a predominance of hormone sensitive breast cancer. Despite stimulating the breast cancer cell growth, HRT has not been shown to increase breast cancer recurrence or mortality when prescribed to breast cancer survivors experiencing oestrogen deficiency symptoms and randomised trials have been recommended and commenced. In conjunction with controlled breast cancer trials demonstrating a therapeutic benefit of high dose estrogens and interest in the use of additive oestrogen therapy in patients developing resistance to oestrogen deprivation, the dogma that HRT is an absolute contra-indication following diagnosis is challenged.     

A hormone from the uterus of the tsetse fly,Glossina morsitans,stimulates parturition and abortion

Unlike most insects, the tsetse female gives birth to a single, fully grown larva at the culmination of each pregnancy cycle. The expulsion of the larva is regulated by a hormone present in rich abundance within the female's uterus. The hormone elicits parturition when injected into neck-ligated females at late stages of pregnancy and abortion when injected at earlier stages. We refer to this highly active material (0.043 uterus equivalents stimulates parturition in 50% of the females) as parturition hormone. Injection of the active extract, which appears to be a peptide or small protein, initiates the series of blood pressure pulsations and uterine contractions normally associated with parturition. The discovery that a uterus extract from the flesh fly also elicits parturition in tsetse suggests that this hormone may be widely distributed in insects.     

Postmenopausal hormone therapy and cognition

This article is part of a Special Issue "Estradiol and cognition".Prior to the publication of findings from the Women's Health Initiative (WHI) in 2002, estrogen-containing hormone therapy (HT) was used to prevent age-related disease, especially cardiovascular disease, and to treat menopausal symptoms such as hot flushes and sleep disruptions. Some observational studies of HT in midlife and aging women suggested that HT might also benefit cognitive function, but randomized clinical trials have produced mixed findings in terms of health and cognitive outcomes. This review focuses on hormone effects on cognition and risk for dementia in naturally menopausal women as well as surgically induced menopause, and highlights findings from the large-scale WHI Memory Study (WHIMS) which, contrary to expectation, showed increased dementia risk and poorer cognitive outcomes in older postmenopausal women randomized to HT versus placebo. We consider the ‘critical window hypothesis’, which suggests that a window of opportunity may exist shortly after menopause during which estrogen treatments are most effective. In addition, we highlight emerging evidence that potential adverse effects of HT on cognition are most pronounced in women who have other health risks, such as lower global cognition or diabetes. Lastly, we point towards implications for future research and clinical treatments.     

Post-menopausal hormone replacement therapy, coronary heart disease and plasma lipoproteins

At least 20 million postmenopausal women worldwide now use some form of hormone replacement therapy. This figure is increasing because the resistance of the medical community to these therapies is diminishing and because of increasing acknowledgement of the benefits of such therapies on the cardiovascular system. This is a remarkable development for a medication originally used to relieve menopausal symptoms such as hot flushes and to prevent bone loss. Although several mechanisms are now accepted to be involved in this protection from cardiovascular disease, changes in plasma lipoproteins remain a major area of research interest. The main issue in this field, whether the addition of a progestogen to postmenopausal oestrogen ('combined therapy') will diminish the benefits on the cardiovascular system, remains unresolved, but combined therapies have now been formulated that minimize the potentially detrimental effects of progestogens on plasma lipoproteins. Recent findings of interest include the effects of these therapies on plasma lipoprotein (a) concentration and on LDL particle size. Studies of the mechanisms behind such changes are needed.     

Eclosion hormone activity in developing embryos of the silkworm, Bombyx mori

The ultimate timing of hatching in the silkworm, Bombyx mori, is controlled by a circadian oscillator. The presence of eclosion hormone in developing embryos of the silkworm is demonstrated. Eclosion hormone activity first becomes detectable in embryos which have developed almost to the stage of the differentiation of the neuroendocrine system. Hormonal activity increases sharply to a maximum level 1 day before hatching and falls by about a half in the newly hatched larvae. Eclosion hormone was partially purified from the pharate first-instar larvae and approx, a 2100-fold purification was achieved. The molecular weight of the embryo eclosion hormone is estimated to be 7000 ～ 9000 Daltons by gel-filtration on Sephadex G-50 (superfine). The role of eclosion hormone on hatching behaviour of the silkworm, Bombyx mori, is discussed.     

Serum hormone patterns during abortion in the Bolivian squirrel monkey

Serum measurements of chorionic gonadotropin (CG), estradiol (E-2) and progesterone (P) were used to describe patterns of hormonal change in Bolivian squirrel monkeys undergoing spontaneous abortion. During early pregnancy, serum CG levels gradually increased, reaching maximum levels at the end of the first 50 days of pregnancy (range: 200-1964 ug protein/ml). E-2 concentrations also increased to high levels (10-30 ng/ml) toward the end of pregnancy, while serum P remained fairly constant at levels above 100 ng/ml. A gradual decline in serum hormone concentrations was observed in aborting animals. CG levels declined to less than 100 ug protein/ml while E-2 and P decreased to concentrations characteristic of nonpregnant cycling animals, less than 500 pg/ml and 20 ng/ml respectively. The data suggest that two weekly measurements of CG and E-2 could be used to identify monkeys undergoing abortion and those which have already aborted.     

Infertility,abortion, and biotechnology

Patterns of reproductive failure described in humans and other mammals suggest that reproductive failure may in many instances be the result of adaptations evolved to suppress reproduction under temporarily harsh conditions. By suppressing reproduction under such conditions, females are able to conserve their time and energy for reproductive opportunities in which reproduction is most likely to succeed. Such adaptations have been particularly important for female mammals, given (a) the amount of time and energy that reproduction requires, and (b) the degree to which reproductive conditions can vary. The existence of conscious and unconscious mechanisms to suppress reproduction under poor conditions has several implications for obstetric/gynecologic practices. Two implications are discussed with reference to biotechnological advancements in our ability to facilitate conceptions and manage problem pregnancies: (a) potential dangers of sophisticated technologies overriding natural fertility controls; and (b) the need for greater appreciation of the association between psychosocial stress and reproductive failure in the treatment of reproductive problems. Implications for elective abortion practices are discussed as well. The ideas for this paper were developed while the author was a recipient of a Career Development Award from the Harry Frank Guggenheim Foundation. Dr. Wasser received a B.S. degree of Zoology from Michigan State University in 1975, a Masters of Science in Zoology from the University of Wisconsin-Milwaukee in 1976, and a Ph.D. in Psychology from the University of Washington in 1981. He is co-director of the Animal Behavior Research Unit, a long-term study on the behavioral ecology and reproduction of free-ranging yellow baboons at Mikumi National Park, Tanzania. Dr. Wasser’s primary research focus is on the evolution of reproductive strategies in female mammals. His work includes research on human infertility and abortion. He is also working on the breeding of endangered species in captivity under a Research Development Award from the National Zoological Park of the Smithsonian Institution.     

Postmenopausal hormone replacement therapy and venous thromboembolism

Background:Women taking hormone replacement therapy (HRT) have a 2- to 5-fold increased risk of venous thrombosis compared with nonusers. Increasingly, evidence has suggested that the size of the risk increase varies according to related factors, such as the type of estrogen used, the mode of delivery, and the presence of other predisposing factors.Objective:The aim of this study was to examine the current literature to assess the varying risk of venous thrombosis among women taking HRT.Methods:An extensive search was carried out on all major electronic databases including MEDLINE 1995 to October 2005 and BIS (EMBASE) 1980 to October 2005. Relevant keywords relating to thrombosis (venous thromboembolism, venous thrombosis, deep vein thrombosis, and pulmonary embolism) combined with hormones (hormone replacement therapy and estrogen) were used to capture all potentially relevant studies.Results:The increased risk of a first episode of venous thrombosis in women currently taking HRT compared with nonusers ranged from 1.22 (95% CI, 0.76–1.94) to 4.50 (95% CI, 1.30–15.10). Similar increases in risks for deep vein thrombosis and pulmonary embolism were found. The risk of venous thrombosis is the highest in the first year of therapy, durich which as much as a greater than 6-fold increase was found. Women taking estrogen-progestin HRT had a significantly greater risk of venous thrombosis than those using estrogen-only preparations (odds ratio [OR], 1.60; 95% CI, 1.13–2.26). Studies have also suggested a dose-related effect, suggesting high-dose estrogen therapy is associated with a greater increased risk of venous thrombosis than low-dose preparations. Comparisons between oral and transdermal HRT have shown a significant difference in the relative risk of venous thrombosis (OR, 4.0; 95% CI, 1.9–8.3) favoring the use of transdermal preparations. The presence of thrombophilia, particularly factor V Leiden, further amplifies the risk of venous thrombosis in women using HRT (OR, 13.16; 95% CI, 4.28–40.47). The presence of other risk factors, such as increasing age and being overweight, were all shown to be associated with a further increase in the risk of venous thrombosis.ConclusionsRecent studies have confirmed that current users of HRT are at increased risk of venous thrombosis. The increase in risk has been shown to vary according to duration of use, with the risk being greatest during the first year of use. Moreover, the increased risk varies according to the type of preparation and presence of additional risk factors such as increasing age, obesity, cancer, and recent surgery. Few studies have examined the relationship between thrombophilia, HRT and venous thrombosis; thus, more research is required in this area before accurate estimates of the risk can be made.     

Growth hormone therapy in achondroplasia

Achondroplasia is one of the most common causes of severe rhizomelic dwarfism. We have previously reported the growth-promoting effect of growth hormone (GH) in this disorder. In this expanded clinical study, dose dependency and the long-term effect of GH were also investigated. Prepubertal children with achondroplasia (82 males and 63 females) were randomly divided into 2 groups. Patients were treated with 0.5 IU/kg per week or 1.0 IU/kg per week subcutaneous recombinant human GH. Of 75 patients, the mutational analysis of fibroblast growth factor receptor-3 revealed that G1138A was detected in 70 and G1138C was found in 2. GH increased growth rate and height z score in a dose-dependent manner. GH also increased serum insulin-like growth factor (IGF)-I, IGF-binding protein-3 and osteocalcin. No adverse effects were observed in either group. We conclude that GH therapy is a useful method for improvement of severe growth retardation of achondroplasia.     

Association of phytoplasmas and viruses with malformed clovers

Plants of Trifolium spp. exhibiting two different kinds of symptoms--phyllody associated with yellowing/reddening, and dwarf growth habit without floral abnormalities--were observed in several areas of the Czechia. Nested polymerase chain reaction (PCR) with phytoplasma specific primers, and restriction fragment length polymorphism (RFLP) analyses of 16SrDNA revealed that phyllody of T. repens was associated with phytoplasmas belonging to the 16SrI-C subgroup. Similar symptoms in T. hybridum and T. pratense plants revealed the presence of phytoplasmas belonging to two subgroups: 16SrI-C and 16SrIII-B. Dwarf disease of cultivated T. pratense plants was associated with more than one agent: 11 of 20 plants examined by PCR/RFLP analysis revealed the presence of phytoplasmas belonging to four distinct subgroups: 16SrI-B, 16SrI-C, 16SrIII-B and 16SrX-A. Moreover, two kinds of bacilliform virions were observed in ultrathin sections of 15 T. pratense plants. Particles occurred mostly in the parenchymatous cells of vascular bundles and were located in the cytoplasm as aggregates within an extended network of membranous cisternae. Phytoplasmas and rhabdoviruses occurred singly, and both together or in co-presence with filamentous virus-like particles.     

Detection of gamma-ray-induced DNA damages in malformed dominant lethal embryos of the Japanese medaka (Oryzias latipes) using AP-PCR fingerprinting.

Adult male fish of the medaka HNI strain exposed to 9.5 Gy or 19 Gy (0.95 Gy/min) of gamma-rays were mated with non-irradiated female fish of the Hd-rR strain. Genomic DNA was prepared from malformed individual embryos which were expected to be dominant lethal and used for AP-PCR fingerprinting. By the use of a part of the T3 promoter sequence (20 mer), which, to our knowledge, is not found in the medaka genome as an arbitrary primer, we found polymorphisms in genomic fingerprints which could distinguish the parental strains. On the other hand, we found that the fingerprints of F1 hybrids were the sum of those of their parents. Based on these findings, we analyzed the fingerprints of genomic DNA of each severely malformed embryo, because we expect that radiation-induced genomic damages resulting in severe malformation and eventually in dominant lethals should be detected as changes in paternal fingerprints of F1 hybrids. Indeed, we succeeded in detecting changes in genomic DNA as loss of some paternal bands in fingerprints of malformed embryos. One of 10 malformed embryos obtained from 9.5 Gy gamma-irradiated males had lost one band of the paternal origin and 4 of 12 malformed embryos obtained from 19 Gy gamma-irradiated males had lost 5 bands. These results indicated a possibility that quantitative as well as qualitative estimation of gamma-ray-induced DNA damages can be made by this method which does not require the functional selection based on a specific target gene.     

孕酮，CA125及TNF-alpha水平与先兆流产的关系

目的：探讨孕酮,CA125 及TNF-alpha水平与先兆流产发生的关系。方法：选择2014 年2 月-2015 年2 月在我院诊断并接受治疗的先兆流产患者60 例,根据妊娠结局不同,将患者分为完成妊娠组和终止妊娠组。另选取同期顺利分娩的产妇作为对照组。比较三组研究对象血清孕酮,CA125 及TNF-琢水平。结果：先兆流产患者血清孕酮水平低于对照组,而CA125 及TNF-alpha水平高于对照组,差异具有统计学意义（P<0.05）;先兆流产终止妊娠组血清孕酮水平低于完成妊娠组,而CA125 及TNF-alpha水平高于完成妊娠组,差异具有统计学意义（P<0.05）。孕酮,CA125 及TNF-alpha水平是先兆流产发生的影响因素（P<0.05）。结论：孕酮水平低,CA125 及TNF-alpha水平高是先兆流产发生的危险因素。临床应给予高度重视,积极采取有效的保胎治疗,避免不良妊娠结局。