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Biomedical subjects

L H Hoffman

Publications and source records attributed to L H Hoffman.

At least 37 records · Page 2Linked to original sources
PubMed1993

Giant and binucleate trophoblast cells of mammals.

The cellular origin, structure, and function of trophoblastic giant cells (GC) and binucleate cells (BNC) are reviewed. Mammals in which these cells have received the greatest attention include rodents, rabbits, and humans (GCs), and ruminants and equids (BNCs). In almost all cases these cells arise from the cytotrophoblast. All are large cells and contain either two diploid nuclei (BNCs), multiple nuclei (human placental bed GCs), or single nuclei with amplified DNA content (rodent and rabbit GCs). Giant and binucleate cells typically exhibit the capacity for migration or invasion, although the degree of migratory activity varies between species. While most end up within, or at the interface with, endometrial tissue, in some instances the GCs or BNCs contribute directly to the interhemal membrane of the placenta. Hormone production is a property which most GC-BNC populations have in common. Lactogen or gonadotropin has been documented in almost all cells of this type examined to date, and in some animals they are also steroidogenic (e.g., rats and sheep). In spite of some common features, both structural and functional differences remain and it is suggested that use of terms such as mononuclear giant cells, multinucleate giant cells, and binucleate cells be continued rather than assuming that these cells are all members of a single trophoblastic subtype.

Animals↗
PubMed1990

Sites of endometrial vascular leakage during implantation in the rabbit.

Vascular labelling with carbon suspension was used to identify endometrial vessels demonstrating macromolecular leakage at implantation sites in the rabbit. Extravasation was seen first in venous components of the deep endometrial stroma on the mesometrial aspect of implantation sites. Carbon labelling was apparent in such vessels at 7 d, 0 hr post coitum, (p.c.), and was attributed to gap formation between endothelial cells. Later in the implantation process, leakage was seen as microextravasations of carbon in the lateral and antimesometrial walls of implantation chambers. Here, penetration of vessels by trophoblast was apparent and membranous processes from the trophoblast projected into vessel lumina. Extravasated material (carbon, platelets) was localized to a labyrinthine system of membranes within the trophoblast, and a potential role for the labyrinth in handling of ingested plasma constituents is discussed. A similar process of trophoblastic penetration of vessels occurred on the mesometrial aspect of implantation sites several hours later. Systemic administration of the anti-inflammatory agent indomethacin blocked vascular leakage due to endothelial gap formation but had little or no effect on trophoblast knob penetration of vessels. This observation may explain the results of previous studies in which treatment with anti-inflammatory agents reduced, but could not inhibit completely, the vascular permeability changes at implantation sites.

Animals↗
PubMed1989

Obplacental giant cells of the domestic rabbit: development, morphology, and intermediate filament composition.

Obplacental giant cells are large (less than or equal to 210 microns) polyploid cells that appear in the stroma of the pregnant uterus of the rabbit following ovoimplantation. Histological examination of a complete developmental series indicates that obplacental giant cells arise from trophoblastic knobs that have traversed the uterine epithelium during early implantation. During maturation, the cells undergo a massive (approximately 6,000%) increase in volume and penetrate deeply into the uterine stroma and myometrium, where they often become associated with blood vessels and smooth muscle cells. Giant cells at mid-gestation contain one or two large nuclei with prominent nucleoli and appear to be amitotic. They are rich in Golgi complexes, RER, SER, and cortically distributed cytoplasmic filaments, and contain intracellular canaliculi lined by microvilli. Giant cells vary with respect to the occurrence of lipid droplets, phagocytotic inclusions, lysosomal structures, and electron-dense granules. Immunocytochemistry demonstrates that the giant cells exhibit intermediate filaments related to cytokeratin and vimentin, but are negative for desmin and for an endothelial cell marker, Factor VIII-related antigen. The cells are positive for cytokeratin from their inception, but only become vimentin-positive between Days 12 and 15 of pregnancy, a change seemingly related to their detachment from epithelial tissue to take on an independent existence. Our findings indicate that the giant cells originate from obplacental trophoblast and, at maturity, exhibit cytoskeletal characteristics of isolated epithelial cells, as well as a complement of organelles suggestive of synthetic activity.

Animals↗
PubMed1989

Active and inactive renin in the adrenal.

Specific renin has been identified in the outer layers of the adrenals of rat, mouse, and human and the inner cortical layers but not in the medulla of mouse adrenals. Nephrectomy causes a marked elevation of adrenal renin, presumably through hyperkalemia. The subcellular distribution of adrenal renin was investigated by Percoll density gradient. The renin activity in the dense granules from the capsules of nephrectomized rats was 15 times greater than that of intact rat. Most of the active form renin was found in dense renin granules. Immunohistochemical studies revealed that the dense granules increased in number after bilateral nephrectomy. Immunogold staining of these granules showed unequivocally the presence of renin therein. Adrenal capsules in organ culture were found to release renin at a steady rate. Renin release from bilaterally nephrectomized rat adrenals was 46 times greater than from the organs of intact animals. The mechanism of the control of renin secretion from the adrenal gland was different from the kidney in that the secretion was stimulated by potassium chloride (10 mol/L) or angiotensin II (10(-9) to 10(-7) mol/L) but not by ACTH (10(-9) to 10(-7) mol/L), suggesting stimulation by intracellular calcium. These results provide evidence that the adrenal synthesizes renin, stores it in specific secretory granules, and secretes it in a regulated manner. Prorenin in the adrenal tissue accounted for only 10% of the total renin whereas 90% of the secreted renin was inactive.

Adrenal Glands↗
PubMed1988

Presence of renin secretory granules in rat adrenal gland and stimulation of renin secretion by angiotensin II but not by adrenocorticotropin.

Renin has been identified biochemically and immunohistochemically in the adrenal gland. We examined the subcellular distribution and behavior of adrenal renin. By differential centrifugation of adrenal capsules, we found renin mainly in mitochondrial fractions. By Percoll density gradient centrifugation of this fraction, dense granules were separated from mitochondria and microsomes. The renin activity in the dense granules from the capsules of nephrectomized rats was 15 times greater than that of the intact rat. Immunohistochemical studies revealed that the dense granules increased in number after bilateral nephrectomy. Immunogold staining of these granules showed unequivocally the presence of renin in these granules. Adrenal capsules in organ culture were found to release renin at a steady rate. Renin release from bilaterally nephrectomized rat adrenals was 46 times faster than from the organs of intact animals. The mechanism of the control of renin secretion from the adrenal gland was different from the kidney in that the secretion was stimulated by potassium chloride (10 mM) or angiotensin II (10(-9)-10(-7) M) but not by ACTH (10(-9)-10(-7) M), suggesting stimulation by intracellular calcium. These results provide evidence that the adrenal synthesizes renin, stores it in specific secretory granules and secretes it in a regulated manner.

Adrenal Cortex↗
PubMed1987

Plasma membrane structure of bat spermatozoa: observations on epididymal and uterine spermatozoa in Myotis lucifugus.

Plasma membrane structure of bat spermatozoa was examined utilizing electron microscopy of thin sections and freeze-fracture replicas. Notable membrane features observed in replicas from cauda epididymal spermatozoa included specialized particle aggregates at the junction between the acrosomal and postacrosomal region of the head (a membrane structure not previously described in mammalian spermatozoa) and another row of rod-like particles just anterior to the posterior ring. Both of these specializations in fractured plasma membranes correspond with regions where the membrane is closely apposed to underlying structures when viewed in thin sections. The postacrosomal sheath appears to be composed of an array of longitudinally oriented filamentous components. Characteristic ordering of intramembranous particles was also noted in replicas from the midpiece region and the annulus. Major changes in plasma membrane structure were not seen in spermatozoa stored in the female reproductive tract; however, the appearance of linear particle aggregations in the principal piece membrane was noted. No evidence was obtained to suggest that an acrosome reaction had occurred in spermatozoa stored in females.

Animals↗
PubMed1987

Secretion of proteins and glycoproteins by perifused rabbit corpus epididymal tubules: effect of castration.

Protein synthesis in epididymal tissue of intact and castrated rabbits was studied after incubation of epididymal minces with [35S]-cysteine or [35S]-methionine and protein separation by two-dimensional gel electrophoresis. Regional differences in the pattern of protein synthesized were observed. Castration did not change overall protein synthesis, but it reduced these regional differences. The presence of 5 alpha-DHT in the culture medium of the proximal corpus epididymidis perfused for 24 hr did not increase overall protein synthesis in tubules from intact or castrated rabbits and did not reinitiate synthesis of the proteins that had disappeared after castration. The kinetics of glycoprotein synthesis and secretion were studied by light and electron microscopy autoradiography at 0.5, 2, 6, and 24 hr after exposure to [3H]-mannose, [3H]-fucose, and [3H]-glucosamine. Changes in the distribution of mannose- and glucosamine-labeled material indicated that the decline in grain density over the epithelium from 30 min to 24 hr coincided with an increasing reaction over the stereocilia border from 30 min to 2 hr and in the lumen from 2 to 24 hr. The distribution of fucose-labeled material indicated that the grain reaction over the epithelium declined more rapidly than with the mannose label. When the glucosamine-labeled sperm mass was released from the tubules, the labeled material was lost after the first washing, indicating that the glucosamine-labeled glycoproteins did not bind firmly to corpus spermatozoa within 24 hr. After castration, both mannose- and fucose-labeled materials migrated to the cell apex more rapidly than in the intact animal, but they were not released as readily into the lumen. The culture of epididymal tubules from castrated males with 5 alpha-DHT for 24 hr did not promote the release of either mannose- or fucose-labeled material into the lumen. However, testosterone given in vivo for 2 weeks restored secretion of mannose-labeled material into the lumen.

Animals↗
PubMed1986

Stage-specific alterations in the apical membrane glycoproteins of endometrial epithelial cells related to implantation in rabbits.

The rabbit endometrial epithelium undergoes differentiation prior to the time of blastocyst implantation, including loss of surface negativity and a change in glycocalyx morphology. Nonpregnant (estrous) and pseudopregnant rabbits were used to study specific alterations in proteins and saccharide composition of the luminal epithelial membrane and its glycocalyx related to the acquisition of receptivity to implantation. Pregnant animals were used to study further modification of the luminal surface by implanting blastocysts. The apical surface of luminal epithelial cells was solubilized by a 15-min intraluminal incubation of 1% Triton X-100 containing protease inhibitors. Proteins in extract solutions were separated by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Three new polypeptides (24 kDa, 42 kDa and 58 kDa) were identified in uteri from receptive rabbits. Binding of succinyl Wheat Germ Agglutinin (sWGA) and Ricinus communis Agglutinin (RCA-I) lectins to the 24 kDa and 42 kDa components on Western blots of extracts separated by SDS-PAGE identified them as glycoproteins. Additionally, other polypeptides (26 kDa, 80-86 kDa and 145 kDa) showed changes in affinity for WGA, RCA-I or concanavalin A (Con A), depending on the hormonal state. Correlating with these findings was an increased binding of these lectins to intact nonciliated cells in uteri of receptive rabbits compared to estrous animals; ciliated cells bound Dolichos biflorus Agglutinin (DBA) specifically, regardless of the hormonal condition. Treatment of uteri from estrous animals, or Western blots of proteins from these animals, with neuraminidase prior to lectin exposure suggested the presence of glycoproteins having a sialic acid-D-galactose terminus in nonreceptive rabbits. Reduced binding of lectin to intact cells at implantation sites and to blots of proteins isolated from these sites, compared to nonimplantation sites, was noted. These results provide evidence for stage-specific alterations in protein and saccharide composition of the apical surface of endometrial epithelium prior to implantation, and indicate that implanting blastocysts further modify the luminal surface.

Animals↗
PubMed1986

Analysis of damage to human ciliated nasopharyngeal epithelium by Neisseria meningitidis.

We used an in vitro model of human nasopharyngeal tissue in organ culture to evaluate the effects of Neisseria meningitidis on human cilia and ciliary function. Encapsulated, viable meningococci damaged ciliated epithelium of nasopharyngeal organ cultures, whereas Neisseria subflava, a commensal species, did not. Meningococcus-induced ciliary damage was due to loss of ciliated cells to which meningococci were not attached. Damage was seen with piliated and nonpiliated meningococci and did not appear to require the presence of other specific meningococcal surface proteins. Meningococcal viability was a requirement for both ciliary damage and interactions of meningococci with microvilli of nonciliated epithelial cells. That is, filter-sterilized supernatants from meningococcus-infected organ cultures, heat-killed meningococci at high inoculum, and purified meningococcal or gonococcal lipopolysaccharide at concentrations of 100 micrograms/ml did not damage ciliary activity of nasopharyngeal organ cultures. In contrast, meningococcal lipopolysaccharide at 10 micrograms/ml markedly damaged ciliary activity of human fallopian tube organ cultures, suggesting a selective toxicity of lipopolysaccharide for specific human ciliated cells. Damage to nasopharyngeal ciliated epithelium by N. meningitidis may be an important first step in meningococcal colonization of the human nasopharynx, but meningococcal lipopolysaccharide does not appear to be directly responsible for this toxicity.

Bacterial Outer Membrane Proteins↗
PubMed1986

The storage form of renin in renin granules from rat kidney cortex.

Renin granules were partially purified from rat kidney cortex, and a storage form of renin in the granules was examined. Renin granules were isolated by discontinuous Percoll density gradient centrifugation followed by continuous Percoll density gradient centrifugation. The partially purified fraction was free from mitochondria and microsomes, as judged by the absence of marker enzymes of these organelles, but contained some lysosomal enzyme activities. The specific renin activity was 0.58 mg angiotensin I/hr/mg protein, 500 times as active as the original homogenate. Immunochemical staining with specific antisera against rat kidney renin revealed that about 10% of the granules recovered in the partially purified fractions were stained strongly. The stored renin was not activated either by acidification or by trypsin treatment, indicating that stored renin was in the fully active form. By sodium dodecyl sulfate gel electrophoresis, the stored renin had two different molecular weights, 38,000 and 36,000, and these molecular weights were not reduced by dithiothreitol or 2-mercaptoethanol, suggesting that these renins are single-chain types as opposed to the two-chain type found in male mouse submaxillary gland. These results suggest that active renins with two different molecular weights may be released from renin granules of juxtaglomerular cells.

Animals↗
PubMed1986

Cytotoxicity and metabolism of alkyl phospholipid analogues in neoplastic cells.

The cytotoxic response of several types of neoplastic cells to analogues of unnatural alkyl phospholipids (e.g., rac-1-hexadecyl-2-methoxy-glycero-3-phosphocholine) has been partially attributed to their accumulation as a result of the low activity of the alkyl cleavage enzyme (a tetrahydropteridine-dependent monooxygenase) in tumor cells. We tested this possibility by comparing the alkyl cleavage enzyme activity in cells that exhibit differences in sensitivity toward the cytotoxic effects of the rac-1-hexadecyl-2-methoxy-glycero-3-phosphocholine. Human promyelocytic leukemia cells (HL-60), a cell line highly sensitive to the cytotoxic alkyl phospholipid analogue, possessed an alkyl cleavage enzyme activity (0.25 pmol/min/microgram protein) similar to that found in three cell types known to be relatively resistant to the cytotoxic activity of the analogue: immature human promyeloblastic leukemia cells (K562) (0.22 pmol/min/microgram protein), human polymorphonuclear neutrophils (0.34 pmol/min/microgram protein), and Madin-Darby canine kidney cells (0.37 pmol/min/microgram protein). Moreover, our results indicate that the cytotoxic rac-1-octadecyl-2-methoxy-glycero-3-phosphocholine analogue is not a substrate for the alkyl cleavage enzyme with an active microsomal preparation of the enzyme from rat liver; cleavage of this analogue was 200-fold less than the rate obtained with 1-octadecylglycerol as substrate. In cultures of either sensitive or resistant type cells, approximately 90% of the added rac-1-[9',10'-3H]octadecyl-2-methoxy-glycero-3-phosphocholine was not metabolized during a 24-h incubation. The amount of radiolabel in fatty acids, a major product of alkyl cleavage activity, was small, and essentially identical amounts were produced in all four cell types [3.1 +/- 0.2% (SD)]. These data indicate that differences in the cellular activities of the alkyl cleavage enzyme are not responsible for the differential cytotoxic responses between normal and specific types of neoplastic cells toward rac-1-octadecyl-2-methoxy-glycero-3-phosphocholine. On the other hand, the cellular uptake of the alkyl phospholipids could be a factor in explaining the cytotoxic response of certain tumor cells, since more radiolabeled 1-octadecyl-2-methoxy-glycero-3-phosphocholine was associated with the susceptible HL-60 cells than with the resistant cell types. Autoradiography revealed that the radiolabeled 2-methoxy analogue accumulates at the periphery of HL-60 leukemia cells, whereas the label was more uniformly distributed in polymorphonuclear neutrophils and K562 cells.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Alterations in epithelial glycocalyx of rabbit uteri during early pseudopregnancy and pregnancy, and following ovariectomy.

Pseudopregnant, pregnant, and ovariectomized rabbits were utilized to study hormonal mediation of uterine epithelial surface negativity and glycocalyx morphology, and to seek local effects of blastocysts at sites of implantatioN. A loss of surface negativity [polycationic ferritin (PCF) binding] by day 6 of pregnancy or pseudopregnancy was noted, accompanied by alterations in epithelial glycocalyx. Uteri from estrous animals, or ovariectomized animals receiving oil or estradiol injections, bound PCF and exhibited a "globular" glycocalyx. Uteri from day 6 pseudopregnant or pregnant animals, or ovariectomized animals receiving progesterone injections, did not bind PCF or exhibit a globular glycocalyx. Both PCF binding and the globular character of the epithelial glycocalyx were sensitive to neuraminidase and trypsin treatment, suggesting sialoglycoprotein contribution to surface negativity. Implanting blastocysts had no detectable local effect on surface negativity, but did induce local reduction of epithelial glycocalyx at sites of implantation. Results of this study suggest that uterine epithelial glycocalyx alterations during the preimplantation period reflect a general response to progesterone stimulation, primarily qualitative in nature, related to the acquisition of receptivity to ovo-implantation.

Animals↗
PubMed1984

Chemotaxis of granulocytes across bovine pulmonary artery intimal explants without endothelial cell injury.

Emigration of granulocytes from vessel lumen to a site of injury is a hallmark of acute inflammation but whether this migration is necessarily associated with vascular damage is not clear. To follow the structural changes associated with granulocyte migration across an intact endothelial cell layer and to assess changes in vascular permeability, an in vitro technique was developed in which intimal explants were stripped from bovine pulmonary artery and mounted in chemotaxis chambers. All explants studied had granulocytes and trace amounts of 3H-water, 14C-sucrose and 125I-albumin in the upper well of the chambers. Experimental explants had zymosan-activated plasma in the lower well and control explants had either serum in the lower well or zymosan-activated plasma in the upper well. Explants were incubated at 37 degrees C for periods from 15 min to 3 hr. When the chemoattractant was added to the lower well, granulocytes migrated into the explants. Transmission and scanning electron microscopy showed an orderly sequence of granulocyte--endothelial interactions throughout which the two cell types maintained close opposition--granulocyte adherence to and exploration of the endothelial surface; penetration and migration through the interendothelial cell junction; reapposition and reformation of the luminal 'tight' junctions and finally passage of granulocytes through the endothelial basal lamina. After 60 min incubation, the majority of granulocytes seen in each section was through the endothelial cell layer and after 2 hr, they were through the basal lamina. Structural evidence of granulocyte or endothelial cell damage was not found at any of the times examined, neither was there any demonstrable increase in intimal permeability. In control explants, granulocyte migration was strikingly less frequent at 2 hr (approximately 10% of that seen towards the chemoattractant). Thus, granulocyte migration across an endothelial cell layer towards a chemoattractant is not necessarily associated with structural evidence of endothelial cell injury or increased vascular permeability.

Animals↗
PubMed1984

Endometrial prostaglandins and phospholipase activity related to implantation in rabbits: effects of dexamethasone.

The anti-inflammatory steroid, dexamethasone, was demonstrated to have an antifertility effect in rabbits when administered systemically on Days 5-7 of pregnancy. The effects of this agent on prostaglandin (PG) concentrations and phospholipase activity in endometrium were determined. Using a highly specific and sensitive gas chromatography-mass spectometry (GC-MS) method, it was established that PGF2 alpha, PGE2 and 6-keto-PGF1 alpha concentrations are all significantly elevated in implant site endometrium relative to nonimplant regions on Day 7 postcoitus (p.c.). Although these levels were strikingly lowered in indomethacin-treated females, the administration of dexamethasone altered the balance between the various PGs but did not reduce tissue levels greatly. Determinations of PG levels in uterine venous plasma likewise demonstrated that neither synthesis nor release of PGs had been drastically curtailed by dexamethasone treatment. Endometrial phospholipase activity was determined on Days 6, 7 and 8 of pregnancy. Enzyme activity was elevated on Day 7 relative to the other days and implant site activity was significantly greater than nonimplant region activity on both Days 6 and 7. Treatment with either dexamethasone or indomethacin reduced the Day 7 activity to baseline levels and obliterated the differential between implant and nonimplant regions. The dexamethasone effect appears to be mediated by induction of a transferable inhibitory factor. Thus, while indomethacin and dexamethasone have similar effects on pregnancy when present during the implantation period, their respective mechanisms of action may be different. Even though dexamethasone inhibits endometrial phospholipase activity, this is not attended by inhibition of PG generation.

6-Ketoprostaglandin F1 alpha↗
PubMed1984

Nuclear matrix antigens in azo dye-induced primary rat hepatomas.

Polyvalent antisera, monoclonal antibodies, and immunotransfer methodology have been used to identify and characterize a group of chromosomal protein antigens which appear during azo dye hepatocarcinogenesis. Experiments were designed to probe for the location and placement of antigens in chromatin according to solubility and possible DNA-binding properties. The majority of nuclear antigens were associated with high-speed DNA-containing pellets after ultracentrifugation of chromatin solubilized with denaturing buffers containing 6 M guanidine-HCl:2% sodium dodecyl sulfate, or 2 M NaCl:5 M urea. The addition of 2-mercaptoethanol or dithiothreitol to guanidine-HCl or sodium dodecyl sulfate solutions resulted in solubilization of nearly all antigens from the DNA pellets, suggesting the presence of complexes (protein:protein and/or DNA:protein) cross-linked with sulfhydryl linkages. Preparation of nuclear matrix from the primary hepatomas under several kinds of conditions indicated these antigens to be components of the residual nuclear matrix, envelope, and/or associated structures. Two-dimensional gel analysis showed most antigens to exist in a range of isoelectric forms, suggesting posttranslational modifications. Studies with monoclonal antibodies prepared to these proteins revealed extensive antigenic homology among the members comprising these fractions. Our results document antigenic differences in the nuclear matrix proteins of primary tumors and their normal tissue counterparts.

Amino Acids↗
PubMed1983

Interaction of Neisseria meningitidis with human nasopharyngeal mucosa: attachment and entry into columnar epithelial cells.

The mechanisms by which Neisseria meningitidis establishes a carrier state or invades mucosal surfaces of the host to cause septicemia and meningitis are unknown. An experimental model of human columnar nasopharyngeal tissue in organ culture was developed, and the interaction of encapsulated, piliated N meningitidis with this mucosal surface was studied. Electron microscopic studies showed that meningococci attached selectively to nonciliated columnar cells of the nasopharynx. After attachment, the microvilli of these nonciliated cells elongated and surrounded the organisms. Six to twelve hours after infection, endocytic vacuoles containing meningococci were seen in the apical portion of some nonciliated columnar cells. Later, diplococci were seen in the subepithelial tissues adjacent to lymphoid tissue; this observation suggested that meningococci had penetrated the epithelial layer. The interaction of meningococci with the nasopharyngeal epithelium may be an important means whereby these bacteria establish a carrier state or invade the host.

Adhesiveness↗
PubMed1983

Effect of histamine receptor antagonists and indomethacin on implantation in the rabbit.

Anti-inflammatory drugs were given to pregnant rabbits during the 24-h period prior to the increase in the uterine vascular permeability which occurs on Day 7. Their effect on the vascular response was monitored by quantifying the concentration of extravascular Evans blue dye. The increase in vascular permeability normally seen on Day 7 was inhibited by either indomethacin or a combination of H1-(mepyramine) and H2-(cimetidine) receptor antagonists. When given alone, neither cimetidine nor mepyramine was as effective as the combination in reducing vascular permeability. Prostaglandins and histamine may be acting together since simultaneous administration of lower doses of indomethacin and the antihistamines reduced vascular permeability below that observed following administration of either class of anti-inflammatory drugs alone. In a second experiment, anti-inflammatory drugs were administered during the peri-implantation period (Days 6-8) and their effect on the weights of maternal and fetal tissues, and on fetal viability were evaluated on Day 14 of pregnancy. Indomethacin had a more deleterious effect on both parameters than did the combination of histamine receptor antagonists. Results from these experiments suggest that both prostaglandins and histamine may participate in the uterine vascular response, whereas the overall process of implantation appears to be more dependent upon the synthesis of prostaglandins than the action of histamine.

Aminopyridines↗