Characterization,localization and actions of endothelins in umbilical vessels and placenta of man

Endothelin-like immunoreactivity was observed in the endothelial lining of umbilical vein and artery as well as in the epithelium of the amniotic membrane. High levels of endothelin-like immunoreactivity (0.4–1.4 pmol g^-1) were detected in human amniotic membrane, umbilical vessels and placenta. The concentration of endothelin-like immunoreactivity in the amniotic fluid was much higher (77 pmol l^-1) than in umbilical cord plasma (10 pmol l^-1). Characterization by reverse phase HPLC revealed that most of the endothelin-like immunoreactivity eluted in the position of synthetic endothelin-1 or oxidized endothelin-1. Specific, high affinity binding sites for endothelin-1 were present in placenta and umbilical artery. Endothelin binding sites were also found in cultured smooth muscle cells from the umbilical artery and vein. In the placenta, endothelin-1 and -3 were almost equipotent as competing ligands for endothelin-1 binding sites, whereas in the umbilical artery endothelin-3 was much less potent than endothelin-1. Scatchard analysis of the binding for placental membranes displayed a straight line (r=–0.994) indicating a single class of endothelin receptors with a K_d-value of 80 pmol l^-1 and B_max of 113 fmol mg^-1. Endothelin-1 caused potent contractions of umbilical arteries and veins with threshold effects at 10 pmol l^-1 while endothelin-3 had no contractile effect up to 10^-7 mol l^-1. It is concluded that endothelin-1 predominates over other endothelins in umbilical vessels, amnion and placenta, and high levels of endothelin-1 was observed in foetal circulation and amniotic fluid. Endothelin-receptors seem to be of different types in placenta (ET_B type) and umbilical vessels (ET_A type).     

Pathomorphology of spiral uterine arteries, umbilical vessels and placenta in disorders of maternal-fetal circulation]

The comparison of the spiral uterine arteries structure, umbilical vessels and placenta is performed in 16 women with normal haemodynamics and in 31 women with disturbances of mother-foetus circulation, and the data obtained were compared with results of dopplerometry made before the delivery. Three clinical groups are distinguished according to the predominant localization of the resistance to the blood flow: the first--with the domination of the spiral arteries obliteration (lack of gestational changes, hyperplastic arteriosclerosis) with a characteristic ultrastructural pathology of the syncytiotrophoblast microvilli, rheological disturbances in the intervillous space and large necroses of villi; the second--with a predominance of early immaturity of the stroma and capillaries or sclerosis and compression of foetal villous capillaries, i. e. with a reduction of a capillary bed and increase of the resistance to the blood flow; the third--with a predominance of the umbilical arteries narrowing and supporting villi and signs of a blood stasis in the foetal veins. Morphologic heterogeneity of the mother--foetus circulation disturbances should be taken into consideration when choosing obstetric tactics.     

Pathology of the placenta. II. Malformations of the umbilical cord and the placenta

Malformations of both the umbilical cord and placenta are covered in the second part of this account of placental pathology. Disorders in placental development are subdivided on the basis of the classification published by Vogel (1984). Particular importance is attributed, in this context, to purely morphological differentiation between hydatid and partial mole. Also discussed is the problem of early placental angiomatosis (chorioangiosis, chorioangiomatosis). However, its association with malformations of the placenta seems to be questionable.     

妊高征胎盘、脐血管中TNF-α表达及组织病理变化的研究

目的研究妊高征患者胎盘和脐血管组织中肿瘤坏死因子(TNF-α)的表达及组织的病理变化情况.方法采用SABC法对轻、中、重度妊高征共27例和正常妊娠组10例的胎盘和脐血管组织进行TNF-α的免疫组化染色,观察各组TNF-α的定位、分布和表达量的差异.同时常规HE染色观察胎盘等形态学变化.结果各组均可见TNF的表达,其定位和分布无差异,主要见于合体滋养细胞、蜕膜细胞、血管内皮细胞和平滑肌细胞等.但中、重度妊高征组TNF的表达量较正常组显著升高(P<0.05,P<0.01).此外,中、重度妊高征组可见细胞滋养细胞增生,合体细胞结节、纤维素样坏死显著增多等病理变化,与正常组相比有显著性差异.结论妊高征时,胎盘、脐血管亦可能是TNF-α的重要产生释放部位.且TNF-α可能通过某些直接或间接的途径,参与了妊高征损伤和代偿并存的复杂变化,在妊高征的发生发展中起着重要作用.     

子痫前期胎盘、脐血管中神经激肽B表达及组织病理变化的研究

目的研究子痫前期患者胎盘、脐血管中神经激肽B（neurok in in B,NKB）的表达及组织的病理变化情况。方法采用SP法对轻、重度子痫前期组共40例和正常妊娠组20例的胎盘和脐血管组织进行NKB的免疫组化染色,观察各组NKB的定位、分布和表达量的差异。同时常规HE染色观察各组胎盘、脐血管的病理变化。结果NKB在各组胎盘合体滋养细胞、毛细血管内皮细胞、脐静脉内皮细胞中均有不同程度的表达。轻、重度子痫前期胎盘组织中,其NKB含量明显高于正常组（P〈0.05,P〈0.01）,HE染色可见子痫前期组细胞滋养细胞增生,合体细胞结节、纤维素样坏死显著增多等病理变化,与正常组相比有显著性差异。结论胎盘可能是NKB的重要产生释放部位。且NKB可能通过某些直接或间接的途径,参与了子痫前期损伤和代偿并存的复杂变化,在子痫前期的发生发展中起着重要作用。     

Immunohistochemical localization of defensin in human coronary vessels.

Neutrophil defensins comprise a family of cationic peptides that possess potent antimicrobial activity. Defensins are normally sequestered in cytoplasmic granules with their primary site of action in phagolysosomes, although some peptide is released into the circulation during the course of infection or inflammation. In view of the fact that neutrophils adhere to the endothelium and that defensins have been reported to bind to human endothelial cells in vitro, we used immunohistochemistry to study the distribution of these peptides in normal and in atherosclerotic human coronary arteries. Defensin was found primarily in the intima of normal and atherosclerotic vessels, most prominently in association with intimal smooth muscle cells. Both large- and small-vessel endothelium stained focally for defensin. Defensin was also found in the media near the external elastic lamina and in some periadventitial vessels. The same distribution was seen in vessels that had been perfusion fixed immediately upon procurement, excluding diffusion of defensin from PMNs ex vivo. These data indicate that neutrophil defensin is present in the walls of human coronary arteries. The deposition of defensin in vessels may contribute to the pathophysiological consequences of inflammation in addition to their role in host defense.     

Dielectric properties of human placenta, umbilical cord and amniotic fluid

The dielectric properties of freshly delivered human placenta, umbilical cord and amniotic fluid have been acquired at 37 °C and in the frequency range of 200 MHz-10 GHz. The experimental data were fitted to a Cole-Cole expression. The results show that dielectric properties of the umbilical cord are significantly higher than placenta due to the presence of high water content Wharton's jelly. The results also demonstrate large differences in the dielectric properties of amniotic and cerebrospinal fluids. The data presented can be used in numerical simulations of the exposure of pregnant women to electromagnetic fields.     

NE and ACh responses of intrapulmonary vessels from dog, swine, sheep, and man.

The effects of norepinephrine (NE) and acetylcholine (ACh) on isometric force generation were studied in isolated helical strips of intrapulmonary arteries (IPA) and veins (IPV) (3-5 mm diam) from lungs of dog, sheep, swine, and man. Cummalative dose-effect relationships (10-minus8-10-minus 4 M) were determined. All strips contracted in a dose-related fashion when exposed to NE but responses of sheep and swineIPV were weak. Acetylcholine relaxed canine IPA and contracted human IPA, CANINEIPV, and sheep IPV in a dose-related manner. Sheep IPA and swine IPA and IPV were unresponsive to ACh. Human IPV were relaxed by ACh but this effect wasreversed at the highest concentration (10 minus 4 M) tested. All vascular stripscontracted well in a potassium-rich (127 mM) bathing medium. It is concluded thatintrapulmonary lobar vessels from man, dog, swine, and sheep are responsive to autonomicneurohormones but that quantitative as well as qualitative differences exist.     

Ultrastructure of newly formed vessels in thrombi. Endothelium formation in human umbilical artery

Thrombi with newly formed vessels in thirteen human umbilical arteries were studied. Red blood cells formed masses which were covered by fibrin within twelve hours after birth. By the second day, the intima including endothelial cells was denuded. In the junctional area between the thrombi and the original intima on the sixth day, red blood cells were surrounded by endothelial-like cells, which displayed junctional complexes and did not show any connection with intact endothelial cells. These cells also exhibited filaments with fusiform densities, suggesting a probable origin from vascular smooth muscle cells. Examination of older specimens indicated that these were precursor structures of functional capillaries found in mature thrombi.     

Ultrastructural localization of glycosaminoglycans in human term placenta

Sulfated glycoconjugates were stained in normal human term placentas using Spicer's high-iron diamine (HID) method with thiocarbohydrazide and silver proteinate (TCH-SP) enhancement. Specific identification of glycosaminoglycans (GAG) was accomplished by digestion of the stained material with chondroitinase ABC or AC for removal of chondroitin sulfates and nitrous acid for removal of N-sulfated GAGs. The syncytiotrophoblast apical surface demonstrated moderate to intense staining with HID-TCH-SP, which was removed by prior digestion with the chondroitinases, but not by nitrous acid. The syncytiotrophoblast basal surface and endothelial cell surfaces lacked sulfate staining. A few cytoplasmic granules in syncytiotrophoblast cells demonstrated staining similar to the apical surface. Three layers of the basal lamina were identified in these preparations. The lamina lucida immediately beneath the syncytiotrophoblast and the majority of the lamina densa stained weakly or not at all, whereas the underlying lamina diffusa and stroma demonstrated moderate to intense staining. The majority of lamina diffusa staining was removed by chondroitinase ABC or AC; the remaining material was removed by nitrous acid digestion. Thus the syncytiotrophoblast surface contains a chondroitin sulfate and the basal lamina contains a mixture of intensely stained chondroitin sulfate and a weakly stained N-sulfated GAG.     

Immunohistochemical localization of androgen receptor in the human endometrium, decidua, placenta and pathological conditions of the endometrium.

The immunohistochemical localization of the androgen receptor in the human endometrium at various stages of the menstrual cycle and post-menopausal period, in decidua and placenta of early pregnancy, and in several pathological conditions of the endometrium has been investigated. At any phase of the menstrual cycle, both endometrial glandular cells and endometrial stromal cells showed positive nuclear staining. Endometrial stromal cells of the functional layer showed stronger staining than those of the basal layer, but endometrial glandular cells of both layers showed the same staining intensity. There was little staining in myometrium. Even after menopause, endometrial glandular and stromal cells showed the same staining pattern as the basal layer of pre-menopausal endometrium and the staining intensity of endometrial stromal cells was weak. In decidua and placenta of early pregnancy, decidual and trophoblastic cells showed positive staining and there was no staining in the stromal cells of placenta. The expression of the androgen receptor was also detected in adenomyosis, endometriosis and endometrial carcinoma. Although the proliferation and differentiation of endometrium are mediated mainly by oestrogen and progesterone receptors, the androgen receptor may play some role in modulating these changes. These results suggest that it may be involved in both physiological and pathological changes of the endometrium.     

Abnormal vessels in the urinary tract following analgesic abuse in man.

A brownish discoloration of the bladder mucosa around the ureteric orifices has been observed on cystoscopy in three patients taking excessive quantities of analgesics. Biopsy specimens revealed an unusual degree of hyalinization of the vessels in the submucosa. Similar changes have been noted in the renal medulla, pelvis, and ureter of patients with classical analgesic nephritis. This vascular change may play an important part in the development of the characteristic infarct-like necrosis seen in the analgesic kidney.     

Apelin和APJ在绒毛及胎盘组织中的表达及意义

目的探讨血管活性肽Apelin及其受体APJ在早期妊娠绒毛和晚期妊娠胎盘组织中的表达和定位。方法分别取10例妊娠7-9w妇女（早孕组）的绒毛组织和15例妊娠37-41w妇女的胎盘组织,采用实时荧光定量逆转录聚合酶链反应法（FO-RT-PCR）及免疫组织化学染色分析法检测两组孕妇胎盘Apelin mRNA及其蛋白的表达情况,并用高清晰度彩色图文分析系统（HPIAS-1000）对其进行定量分析。结果FQ-RT-PCR结果显示,足月妊娠胎盘Apelin mRNA显著高于早孕绒毛组织（P〈0.05）。免疫组化及高清晰度彩色图文分析系统结果显示,Apelin-36和APJ蛋白在早孕绒毛组织和足月妊娠胎盘组织中均有表达,二者在早孕绒毛组织中的表达部位主要位于绒毛内滋养细胞：在足月妊娠胎盘组织中,主要表达于胎盘合体滋养细胞及血管内皮细胞Apelin在足月妊娠胎盘组织中的表达强度要高于早孕绒毛组织,有极显著性差异（P〈0.01）,而APJ在早孕绒毛组织和足月妊娠胎盘组织中的表达强度无明显差异（P〉0.05）。结论Apelin在晚孕胎盘组织中表达增强,Apelin/APJ可能在子宫-胎盘血管的发育及功能调控过程中发挥重要作用。     

Ultracytochemical localization of adenylate cyclase in early human placenta

A cytochemical study was carried out on adenylate cyclase (AC) activity in the early human placenta. Samples of placental villi were incubated in a medium containing adenylyl-imidodiphosphate (AMP-PNP) as specific substrate. No AC reaction product was encountered in placenta villi taken at 5 and 7 weeks of pregnancy. AC activity appeared at 9 weeks. At 9 and 10 weeks, AC reaction product was localized on the basal plasma membranes and on apposed plasma membranes of the Langhans cytotrophoblast. At 11 weeks AC activity was also clearly visible on Langhans cytotrophoblast and syncytiotrophoblast apposed plasma membranes. No AC reaction product was ever detected on the syncytiotrophoblast microvillar membrane. These results are in agreement with biochemical studies that localize AC on the villous trophoblast plasma membranes associated with the fetal circulation.