Normal Villi Research Articles

Placental mesenchymal dysplasia, a case of intrauterine sudden death in a normal-sized fetus

placental mesenchymal dysplasia (PMD) is a rare placental anomaly characterized by placentomegaly and grape-like vesicles which resemble molar pregnancy. we report the case of 33-year-old woman (1-gravid) who visited our clinic at 11 weeks of gestation due to a suspected molar pregnancy. Ultrasound examination showed an enlarged placenta with multiple vesicular lesions. Maternal human chorionic gonadotropin level was normal and chorionic villus sampling showed a normal male karyotype (46 XY). The fetus exhibited no specific anomalies and fetal growth was normal during pregnancy with no signs of fetal suffering. At 31 weeks, the pregnancy ended owing to intrauterine fetal death (IUFD). The patient delivered a normal-sized male fetus (1800 g) with no definite anomalies. A pathological examination led to a diagnosis of placental mesenchymal dysplasia. in the presence of placental ultrasound anomalies with no other sign of fetal suffering, the pregnancy should be considered at risk and, therefore, should be monitored carefully including the option of hospitalization.

Kruppel-like factor 5 controls villus formation and initiation of cytodifferentiation in the embryonic intestinal epithelium

Kruppel-like factor 5 (Klf5) is a transcription factor expressed by embryonic endodermal progenitors that form the lining of the gastrointestinal tract. A Klf5 floxed allele was efficiently deleted from the intestinal epithelium by a Cre transgene under control of the Shh promoter resulting in the inhibition of villus morphogenesis and epithelial differentiation. Although proliferation of the intestinal epithelium was maintained, the expression of Elf3, Pparγ, Atoh1, Ascl2, Neurog3, Hnf4α, Cdx1, and other genes associated with epithelial cell differentiation was inhibited in the Klf5-deficient intestines. At E18.5, Klf5Δ/Δ fetuses lacked the apical brush border characteristic of enterocytes, and a loss of goblet and enteroendocrine cells was observed. The failure to form villi was not attributable to the absence of HH or PDGF signaling, known mediators of this developmental process. Klf5-deletion blocked the decrease in FoxA1 and Sox9 expression that accompanies normal villus morphogenesis. KLF5 directly inhibited activity of the FoxA1 promoter, and in turn FOXA1 inhibited Elf3 gene expression in vitro, linking the observed loss of Elf3 with the persistent expression of FoxA1 observed in Klf5-deficient mice. Genetic network analysis identified KLF5 as a key transcription factor regulating intestinal cell differentiation and cell adhesion. These studies indicate a novel requirement for KLF5 to initiate morphogenesis of the early endoderm into a compartmentalized intestinal epithelium comprised of villi and terminally differentiated cells.

Image-Enhanced Endoscopy with I-scan Technology for the Evaluation of Duodenal Villous Patterns

I-scan technology is the newly developed endoscopic tool that works in real time and utilizes a digital contrast method to enhance endoscopic image. We performed a feasibility study aimed to determine the diagnostic accuracy of i-scan technology for the evaluation of duodenal villous patterns, having histology as the reference standard. In this prospective, single center, open study, patients undergoing upper endoscopy for an histological evaluation of duodenal mucosa were enrolled. All patients underwent upper endoscopy using high resolution view in association with i-scan technology. During endoscopy, duodenal villous patterns were evaluated and classified as normal, partial villous atrophy, or marked villous atrophy. Results were then compared with histology. One hundred fifteen subjects were recruited in this study. The endoscopist was able to find marked villous atrophy of the duodenum in 12 subjects, partial villous atrophy in 25, and normal villi in the remaining 78 individuals. The i-scan system was demonstrated to have great accuracy (100 %) in the detection of marked villous atrophy patterns. I-scan technology showed quite lower accuracy in determining partial villous atrophy or normal villous patterns (respectively, 90 % for both items). Image-enhancing endoscopic technology allows a clear visualization of villous patterns in the duodenum. By switching from the standard to the i-scan view, it is possible to optimize the accuracy of endoscopy in recognizing villous alteration in subjects undergoing endoscopic evaluation.

The Significance of Duodenal Mucosal Atrophy in Patients With Common Variable Immunodeficiency

Gastrointestinal manifestations and villous atrophy can be seen in patients with common variable immunodeficiency (CVID). In some patients, infectious agents may be responsible, whereas in others, celiac disease (CD) may be the cause. In this study, we investigate the causes and the histopathologic features seen in patients with CVID. Eleven patients with CVID and villous atrophy underwent duodenal biopsies, human leukocyte antigen (HLA) typing, and testing for all celiac antibodies. Fifteen patients with CVID and normal villi and 6 patients with CD but without CVID served as controls. Histologic response to a gluten-free diet (GFD) allowed a diagnosis of CD in 3 of 11 patients. In the remaining 8, the lack of a histologic response to a GFD or HLA typing excluded CD. Celiac antibodies gave conflicting results and were of no help. Polymorphonuclear infiltrates and lesions like graft-versus-host disease are seen more often in flat mucosa unresponsive to a GFD. However, the specificity of these findings remains to be determined and response to a GFD remains the only diagnostic criteria for CD in these patients. Villous atrophy was gluten-sensitive in 3 of 11 patients with CVID. It was not related to gluten-responsive CD in most patients.

Short tandem repeat analysis for diagnosing complete hydatidiform mole and coexisting fetus: a casereport and literature review

Objective To investigate the parental origin for a rare case of complete hydatidiform mole and coexisting fetus and to discuss its diagnosis and differential diagnosis.Methods Tissues from the fetus,mole and placenta were collected and pathology analysis and chromosome analysis were done.The DNA from the fetus,mole and parents' peripheral blood leukocytes was amplified with five short tandem repeat (STR) markers (D4S2460,D18S488,D21S2039,DXS1205 and DYS219) at the same time to confirm the parental source of the hydatidiform.Results (1) Casereport:A 27-year-old woman,gravida 1,para 0,was found high risk for neural tube defects at 20 weeks of gestation.At 24+5 weeks of gestation,ultrasound examination demonstrated a normal fetus,a normal placenta and a huge mass with a multicystic appearance attached to the placenta with an obvious demarcation.The fetus died at 26 weeks of gestation.Serum human chorionic gonadotropin-β(β -hCG) level decreased obviously during the first two weeks after artificial induction,but elevated at the third week,and β-hCG titers fell to normal after 2 courses of chemotherapy.Fetus autopsy showed no structure abnormality.Histopathologic examination of the hydatidiform showed swelling of chorionic villi with hyperplasia of the trophoblast and formation of central cisterns suggesting of a twin pregnancy consisting of a complete hydatidiform mole and coexisting fetus.(2) Genetic analysis:The karyotype analysis of the normal placental villi was 46,XY; the cell cultures of fetal cartilage tissue and hydatidiform were failed.STR analysis showed that the fetus was diploid from biparental source;the mole was androgenetic source.And the mole had locus both from Y and X chromosome of the father,so it was heterozygous.It was suggested that this case was derived from one single oocyte fertilized with three spermatozoas.Conclusions STR analysis could be used to confirm the diagnosis of complete hydatidiform mole and coexisting fetus and to find the pathogenetic rnechanism. Key words: Hydatidiform mole; Microsatellite repeats; Heterozygote; Ultrasonography, prenatal

The branching pattern of villous capillaries and structural changes of placental terminal villi in type 1 diabetes mellitus

Maternal diabetes is associated with changes of the placental structure. These changes include great variability of vascularity manifested by strikingly hypovascular as well as hypervascular terminal villi. In this paper, normal placental terminal villi and pathological villi of type 1 diabetic placentas were compared concerning the structure of villous stroma, spatial arrangement of villous capillary bed and quantitative assessment of capillary branching pattern.Formalin fixed and paraffin embedded specimens of 14 normal and 17 Type 1 diabetic term placentas were used for picrosirius staining, vimentin and desmin immunohistochemistry and confocal microscopy. 3D models of villi and villous capillaries were constructed from stacks of confocal optical sections.Hypervascular as well as hypovascular villi of diabetic placenta displayed changed structure of villous stroma, i.e. the collagen envelope around capillaries looked thinner and the network of collagen fibers seemed less dense. The desmin immunocytochemistry has shown that stromal cells of hypervascular as well as hypovascular villi appeared nearly or completely void of desmin filaments. In comparison with normal villi, capillaries of hypovascular villi had a smaller diameter and displayed a markedly wavy course whereas in hypervascular villi numerous capillaries occurred in reduced stroma and often had a large diameter. The quantitative assessment of capillary branching has shown that villous capillaries are more branched in diabetic placentas.It is concluded that type 1 maternal diabetes enhances the surface area of the capillary wall by elongation, enlargement of diameter and higher branching of villous capillaries and disrupts the stromal structure of terminal villi.

Immunohistochemistry of p57 and p53 protein in differential diagnosis of hydropic abortion, partial and complete hydatidiform mole

To investigate the role of p57 and p53 immunohistochemistry in the differential diagnosis of hydropic abortion, partial hydatidiform mole and complete hydatidiform mole. Immunohistochemical stains (EnVision method) for p57 and p53 were performed in tissue samples of normal placenta chorionic villi (n=10), abortion chorionic villi (n=12), partial hydatidiform (n=23) and complete hydatidiform moles (n=20). The expression of p57 was predominantly localized in the nuclei of villous cytotrophoblasts and stromal cells. The positive rates of p57 in normal placenta, hydropic abortion and partial hydatidiform mole were 10/10, 12/12, and 100% (23/23), respectively, with no significant difference among the groups (P>0.05). However, none of the complete hydatidiform moles analyzed exhibited p57 positivity in cytotrophoblasts and stromal cells. There was a significant difference between partial and complete hydatidiform moles (P<0.05). The expression of p53 was observed in the nuclei of cytotrophoblastic cells and intermediate trophoblasts. No p53 expression was seen in normal placenta and only 1 of 12 hydropic abortion showed p53 positivity. The positive rates of p53 expression in partial and complete hydatidiform mole were 60.9% (14/23) and 85.0% (17/20) respectively. It was significantly higher in partial hydatidiform mole than that in hydropic abortion. A significant difference was also found between partial and complete hydatidiform moles (P<0.05). Our findings confirm that p57 immunohistochemistry assists the differential diagnosis of complete hydatidiform mole from partial hydatidiform mole. Expression of p53 may be helpful in distinguishing partial hydatidiform mole from hydropic abortion.

Expression and significance of LMP2 and PPM1A in gestational trophoblastic disease

To investigate the expression of low molecular mass polypeptide-2 (LMP2) and protein phosphatase 1A (PPM1A) in gestational trophoblastic disease and elucidate their predictive value in malignant transformation of hydatidiform mole. The expressions of LMP2 and PPM1A protein in 196 complete hydatidiform moles (in which 28 cases with malignant transformation), 7 invasive moles, 5 choriocarcinomas and 20 normal chorionic villus were detected with the method of EnVision immunohistochemistry. Their clinicopathologic data were retrospectively analyzed. LMP2 and PPM1A protein expressed in cytotrophocytes, syncytiotrophoblast and extravillous trophoblast. The level of LMP2 expression in deteriorative hydatidiform mole was significantly higher than that in non-deteriorative hydatidiform mole or normal chorionic villus (6.79±2.38, 5.26±2.63 and 3.10±1.65, all P<0.01), while there were no difference compared with gestational trophoblastic neoplasms (6.42±2.68, P=0.113). The level of PPM1A expression was highest in normal chorionic villus, and decreased gradually in hydatidiform mole (non-deteriorative and deteriorative) and gestational trophoblastic neoplasms (6.30±2.98, 4.93±2.50, 4.43±2.04 and 3.33±2.06, all P<0.01); the level of PPM1A expression in deteriorative hydatidiform mole was significantly lower than that in non-deteriorative hydatidiform mole (P=0.001). The expression of LMP2 protein was correlated to theca lutein ovarian cyst, the expression of PPM1A protein was related with uterine size (P<0.05). While, there was no correlation between the expressions of the two proteins (P>0.05). High expression of LMP2 and low expression of PPM1A might play an important role in the motility and invasiveness of trophoblast cells and malignant transformation of hydatidiform mole. Testing the expression of LMP2 and PPM1A in hydatidiform mole tissues of initial uterine evacuation might be have some reference significance in judging outcomes of hydatidiform mole.

Current spectrum of malabsorption syndrome in adults in India

Tropical sprue was considered to be the most important cause of malabsorption in adults in India. However, several reports indicate that celiac disease is now recognized more frequently. We analyzed the clinical presentation, endoscopic and histological features of 94 consecutive patients (age >12 years) with chronic diarrhea and malabsorption syndrome. The spectrum of disease in these patients and features differentiating celiac disease and tropical sprue are reported here. Celiac disease (n = 61, 65%) was the most common cause of malabsorption followed by tropical sprue (21, 22%). Other conditions including cyclosporiasis (3), Crohn's disease (2), common variable immunodeficiency (2), lymphangiectasia (1), William's syndrome (1), and idiopathic malabsorption (3) accounted for the remainder. A greater number (21, 34%) of patients with celiac disease than those with tropical sprue (4, 19%) presented with atypical manifestations. Patients with celiac disease were younger (p = 0.001), more often had anemia, (p = 0.001), scalloping of folds (p = 0.001), moderate (p = 0.02) or severe (p = 0.001) villous atrophy, higher grade of intraepithelial lymphocytic infiltration (p = 0.001), crypt hyperplasia (p = 0.001), cuboidal (p = 0.001) and pseudostratified (p = 0.009) surface epithelial cells, and diffuse (p = 0.001) epithelial damage. In comparison, patients with tropical sprue were older and more often had normal duodenal folds, normal villi, tall columnar epithelial cells and focal epithelial damage. Celiac disease was the most frequent cause of malabsorption syndrome in this series of patients. There are significant clinical and histological differences between celiac disease and tropical sprue.

Studies on a Novel Serine Protease of a ΔhapAΔprtV Vibrio cholerae O1 Strain and Its Role in Hemorrhagic Response in the Rabbit Ileal Loop Model

BackgroundTwo well-characterized proteases secreted by Vibrio cholerae O1 strains are hemagglutinin protease (HAP) and V. cholerae protease (PrtV). The hapA and prtV knock out mutant, V. cholerae O1 strain CHA6.8ΔprtV, still retains residual protease activity. We initiated this study to characterize the protease present in CHA6.8ΔprtV strain and study its role in pathogenesis in rabbit ileal loop model (RIL).Methodology/Principal FindingsWe partially purified the residual protease secreted by strain CHA6.8ΔprtV from culture supernatant by anion-exchange chromatography. The major protein band in native PAGE was identified by MS peptide mapping and sequence analysis showed homology with a 59-kDa trypsin-like serine protease encoded by VC1649. The protease activity was partially inhibited by 25 mM PMSF and 10 mM EDTA and completely inhibited by EDTA and PMSF together. RIL assay with culture supernatants of strains C6709 (FA ratio 1.1+/−0.3 n = 3), CHA6.8 (FA ratio 1.08+/−0.2 n = 3), CHA6.8ΔprtV (FA ratio 1.02+/−0.2 n = 3) and partially purified serine protease from CHA6.8ΔprtV (FA ratio 1.2+/−0.3 n = 3) induced fluid accumulation and histopathological studies on rabbit ileum showed destruction of the villus structure with hemorrhage in all layers of the mucosa. RIL assay with culture supernatant of CHA6.8ΔprtVΔVC1649 strain (FA ratio 0.11+/−0.005 n = 3) and with protease incubated with PMSF and EDTA (FA ratio 0.3+/−0.05 n = 3) induced a significantly reduced FA ratio with almost complete normal villus structure.ConclusionOur results show the presence of a novel 59-kDa serine protease in a ΔhapAΔprtV V. cholerae O1 strain and its role in hemorrhagic response in RIL model.

Hydrogen Sulfide Attenuates Ischemia-Reperfusion Injury in In Vitro and In Vivo Models of Intestine Free Tissue Transfer

Ischemia-reperfusion injury is the propagation of injury following reintroduction of oxygen to previously ischemic tissue. The purpose of this study was to evaluate whether hydrogen sulfide provides protection against ischemia-reperfusion injury in enteric tissue. In vitro (enterocyte anoxia-normoxia) and in vivo (rat intestinal ischemia-reperfusion) models of ischemia-reperfusion injury were tested with or without the addition of hydrogen sulfide. Apoptotic index was determined in vitro, and gross appearance, histology, and villus height (a measure of mucosal integrity) were assessed in vivo. Statistical analysis was performed, and significance was defined as p < 0.05. In vitro, cells treated with 10 microM hydrogen sulfide after 1-hour anoxia experienced a significant decrease in apoptotic index compared with untreated control (0.5 +/- 0.3 percent versus 2.8 +/- 0.7 percent); after 3 hours of anoxia, cells treated with 1 microM, 10 microM, and 100 microM hydrogen sulfide experienced significant decreases in apoptotic index versus untreated control (1.6 +/- 0.8 percent, 1.8 +/- 0.9 percent, and 2.8 +/- 0.7 percent versus 8.6 +/- 1.7 percent). In vivo, intestine treated with [10 microM] or [100 microM] hydrogen sulfide retained normal coloration and villus architecture after 1-hour ischemia; after 2 hours of ischemia, only intestine treated with [10 microM] hydrogen sulfide appeared uninjured. After 1, 2, or 3 hours of ischemia, villus heights of intestine treated with [10 microM] or [100 microM] hydrogen sulfide were significantly higher than heights of non-hydrogen sulfide-treated villi. Hydrogen sulfide significantly attenuates ischemia-reperfusion injury in intestinal tissue in vitro and in vivo. These results have significant implications for enteric free tissue transfers and other gastrointestinal procedures in which ischemic intervals may be anticipated.

Studies on Hofbauer cells in villous stroma of hydatidiform mole.

Studies on stromal cells of chorionic villi, whose functions are still unknown, lag behind investigations on trophoblasts. Hofbauer cells were examined by light and electron microscopy, and the frequency of their appearance in 31 cases of normal villi was compared with that in 9 cases of hydatidiform moles and 6 of invasive moles. The uptake of 3H-thymidine was also examined. Morphologically and functionally, it was suggested that Hofbauer cells in the villous stroma possessed macrophage-like characteristics.

Celiac Disease without Villous Atrophy in Children: A Prospective Study

To establish whether children who are endomysial antibody (EmA) positive and have normal small-bowel mucosal villous morphology are truly gluten-sensitive and may benefit from early treatment with a gluten-free diet. Children who were EmA positive with normal small-bowel mucosal villi were compared with children who were seropositive with villous atrophy by using several markers of untreated celiac disease. Thereafter, children with normal villous structure either continued on a normal diet or were placed on a gluten-free diet and re-investigated after 1 year. Seventeen children who were seronegative served as control subjects for baseline investigations. Normal villous morphology was noted in 17 children who were EmA positive, and villous atrophy was noted in 42 children who were EmA positive. These children were comparable in all measured variables regardless of the degree of enteropathy, but differed significantly from the seronegative control subjects. During the dietary intervention, in children who were EmA positive with normal villi, the disease was exacerbated in children who continued gluten consumption, whereas in all children who started the gluten-free diet, both the gastrointestinal symptoms and abnormal antibodies disappeared. The study provided evidence that children who are EmA positive have a celiac-type disorder and benefit from early treatment despite normal mucosal structure, indicating that the diagnostic criteria for celiac disease should be re-evaluated.

Gastrointestinal symptoms, quality of life and bone mineral density in mild enteropathic coeliac disease: A prospective clinical trial

Objective. The diagnosis of coeliac disease requires small-bowel mucosal villous atrophy with crypt hyperplasia. However, patients with endomysial antibodies but structurally normal villi may suffer from a disorder similar to those with villous atrophy. The aim of this study was to evaluate gastrointestinal symptoms, quality of life and bone mineral density in patients with mild enteropathy, and the effect of a gluten-free diet. Material and methods. A prospective trial was carried out in 73 adults having endomysial antibodies with normal villous morphology (Marsh I–II; mild enteropathy) or villous atrophy (Marsh III). Gastrointestinal symptoms and quality of life were surveyed by means of structured questionnaires and bone mineral density by means of X-ray absorptiometry. Altogether, 110 subjects served as non-coeliac controls. Results. At baseline, patients with mild enteropathy evinced more gastrointestinal symptoms than non-coeliac controls, but there were no significant differences in quality of life between the groups. After 1 year on a gluten-free diet, indigestion and depression were significantly alleviated in the mild enteropathy group. Osteoporosis or osteopenia was detected in 58% of subjects in the mild enteropathy group and there was a trend towards improved bone mineral density after the treatment. Conclusions. Endomysial antibody-positive patients with normal villous structure may suffer from gastrointestinal symptoms and have poor bone health. Furthermore, they benefit from a gluten-free diet similar to those with overt villous atrophy.

Hemidesmus indicus R. Br. root extracts reduce Salmonella typhimurium - induced inflammation in rat intestine by repressing its type three secretory proteins

Emergence of multidrug resistant bacterial strains urged the investigation for alternative medicines. The present study was designed to evaluate the mode of action of the crude methanolic extract of Hemidesmus indicus root againstSalmonella typhimurium both in vivo and in vitro. Pounded root was soaked in methanol for 7 days in room temperature with three solvent changes. The extract was pooled together, distilled and concentrated. An insoluble fraction comprising terpenoides, steroids and fatty acids, abbreviated as ME1 (methanol extract 1) was isolated from the crude methanol extract of H. indicus root (MHI with tannins and glycosides as the major constituents) during extraction. This study deals with the effect of these crude extracts (ME1 and MHI) against S. typhimurium-induced pathogenesis. In vivo ileal loop model in rat, in vitro organ culture and in vivo multiplication of S. typhimurium were used in mouse model (n=6). Both ME1 and MHI treated bacteria had 3 - 4 foldless initial attachment to murine intestinal epithelium in comparison to the wild type bacteria. The in vivo multiplication rate of wild S. typhimurium in the liver and spleen of mice was 100 fold higher, which was considerably less for MHI treated bacteria and negligible for ME1 treated S. typhimurium. The rat ileum infected with wild bacteria was severely inflamed; whereas the ileum infected with ME1 treated S. typhimuriumwas almost normal in appearance. The rats pre administered with MHI and then infected with wild type bacteria had normal villi, which proved its protective role. The in vivo activity of the extracts was further confirmed in vitro by using various simulating growth conditions, which mimic host environment. The type III secretory proteins (TTSPs) were isolated from wild as well as extract treated S. typhimurium and compared. Both the extracts inhibited the secretory proteins encoded by SPI-1 (involved in invasion and enteritis) as well as SPI-2 (involved in intracellular survival and multiplication) considerably. Differential activity of different constituents was observed to protect rat intestine as MHI had prophylactic and ME1 had therapeutic activity. Key words: Hemidesmus indicus root, ME1, MHI, SPI-1, SPI-2, Salmonellatyphimurium, type III secretory proteins (TTSPs).

Index of Suspicion

Index of Suspicion

Placental mesenchymal dysplasia: a potential misdiagnosed entity

Placental mesenchymal dysplasia is a rare condition characterized by enlarged multicystic placenta with anechoic regions on ultrasound. Gross examination shows grapelike vesicles which mimics molar pregnancy. Microscopic findings shows large edematous villi with cistern formation interspersed with normal villi. The absence of trophoblastic proliferation and trophobastic inclusions differentiates it from molar pregnancy. We report a new case of placental mesenchymal dysplasia. A 31-year-old G2P1 presented with preterm vaginal bleeding at 24 5/7 weeks of gestation. Ultrasound findings show cystic placenta and placenta previa. She went into preterm labor and delivered a female baby with no dysmorphic features but later suffered from complications of prematurity. Pathologically, the placenta showed multiple grapelike cystic vesicles with unremarkable chorionic vessels. Microscopically, enlarged edematous villi with cistern formation were noted. Trophoblastic proliferation or inclusions were not seen.

Gluten‐dependent Small Bowel Mucosal Transglutaminase 2–specific IgA Deposits in Overt and Mild Enteropathy Coeliac Disease

In coeliac disease, immunoglobulin (Ig)A-class autoantibodies against transglutaminase-2 are produced in the small intestinal mucosa, where they are deposited extracellularly. It remains unclear whether positive intestinal transglutaminase-2-targeted IgA deposits in subjects having normal small bowel mucosal morphology are signs of early-stage coeliac disease. We evaluated the gluten dependency of these deposits in overt and mild enteropathy coeliac disease. All together 48 subjects suspected of coeliac disease but having normal small bowel mucosal villi were enrolled; 28 of them had latent coeliac disease. The remaining 20 having positive intestinal IgA deposits adopted a gluten-free diet before villous atrophy had developed. For comparison, 13 patients with overt coeliac disease and 42 noncoeliac controls were studied. Small bowel mucosal transglutaminase-2-specific autoantibodies were compared with villous morphology, intraepithelial lymphocyte densities, and serum coeliac autoantibodies. Intestinal IgA deposits were seen in all but 1 of the patients with latent coeliac disease, when the morphology was still intact; the intensity of these deposits increased as villous atrophy developed and decreased again on a gluten-free diet. In 20 patients with intestinal IgA deposits in normal villi, the intensity of the deposits decreased with the diet similarly to that seen in patients with overt coeliac disease. Mucosal IgA deposits were seen initially only in 5% of noncoeliac controls and in 8% after extended gluten consumption. The response of small bowel mucosal transglutaminase-2-specific IgA deposits for dietary intervention was similar in overt and mild enteropathy coeliac disease. Detection of such IgA deposits thus offers a good diagnostic tool to uncover early-stage coeliac disease.

Protein S deposition at placenta: a possible role of protein S other than anticoagulation

Protein S is an antithrombotic cofactor for protein C that also has multifunctional anti-inflammatory, cellular protective, apoptotic and mitogenic properties. Protein S levels are thought to decrease during pregnancy, but the underlying mechanism remains unknown. We compared protein S concentrations throughout normal pregnancy with those of nonpregnant women and measured plasma C4b-binding protein levels in nonpregnant women and in pregnant women at the 40th gestational week. We also examined protein S and C4b-binding protein in the placenta by immunohistochemical staining at early (20th gestational week) and late (40th gestational week) stages of pregnancy. Plasma protein S activity and free protein S-antigen levels significantly decreased from the 10th gestational week and total protein S antigen decreased from the 20th. C4b-binding protein levels between pregnant and nonpregnant women did not significantly differ. The stainable portion of protein S was located at the fetomaternal interface, particularly at degenerative villi. C4b-binding protein was weakly stained at the same areas as protein S. Neither protein S nor C4b-binding protein were stained at normal villi. These results indicated that protein S can protect or restore damaged villi via a physiological effect in addition to its anticoagulation properties.

Normal chorionic villus sampling after tetraploid karyotype found on trophectoderm biopsy

Normal chorionic villus sampling after tetraploid karyotype found on trophectoderm biopsy