The Experts below are selected from a list of 297 Experts worldwide ranked by ideXlab platform
Peter M Elias - One of the best experts on this subject based on the ideXlab platform.
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mechanisms of abnormal Lamellar Body secretion and the dysfunctional skin barrier in patients with atopic dermatitis
The Journal of Allergy and Clinical Immunology, 2014Co-Authors: Peter M Elias, Joan S WakefieldAbstract:I review how diverse inherited and acquired abnormalities in epidermal structural and enzymatic proteins converge to produce defective permeability barrier function and antimicrobial defense in patients with atopic dermatitis (AD). Although best known are mutations in filaggrin (FLG) , mutations in other member of the fused S-100 family of proteins (ie, hornerin [hrn] and filaggrin 2 [flg-2]); the cornified envelope precursor (ie, SPRR3); mattrin, which is encoded by TMEM79 and regulates the assembly of Lamellar bodies; SPINK5 , which encodes the serine protease inhibitor lymphoepithelial Kazal-type trypsin inhibitor type 1; and the fatty acid transporter fatty acid transport protein 4 have all been linked to AD. Yet these abnormalities often only predispose to AD; additional acquired stressors that further compromise barrier function, such as psychological stress, low ambient humidity, or high-pH surfactants, often are required to trigger disease. T H 2 cytokines can also compromise barrier function by downregulating expression of multiple epidermal structural proteins, lipid synthetic enzymes, and antimicrobial peptides. All of these inherited and acquired abnormalities converge on the Lamellar Body secretory system, producing abnormalities in lipid composition, secretion, and/or extracellular Lamellar membrane organization, as well as antimicrobial defense. Finally, I briefly review therapeutic options that address this new pathogenic paradigm.
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ichthyosis in sjogren larsson syndrome reflects defective barrier function due to abnormal Lamellar Body structure and secretion
Archives of Dermatological Research, 2010Co-Authors: William B Rizzo, Mary L Williams, Dana Saulis, Anitia M Jennings, D Crumrine, Peter M EliasAbstract:Sjogren–Larsson syndrome is a genetic disease characterized by ichthyosis, mental retardation, spasticity and mutations in the ALDH3A2 gene coding for fatty aldehyde dehydrogenase, an enzyme necessary for oxidation of fatty aldehydes and fatty alcohols. We investigated the cutaneous abnormalities in 9 patients with Sjogren–Larsson syndrome to better understand how the enzymatic deficiency results in epidermal dysfunction. Histochemical staining for aldehyde oxidizing activity was profoundly reduced in the epidermis. Colloidal lanthanum perfusion studies showed abnormal movement of tracer into the extracellular spaces of the stratum corneum consistent with a leaky water barrier. The barrier defect could be attributed to the presence of abnormal Lamellar bodies, many with disrupted limiting membranes or lacking Lamellar contents. Entombed Lamellar bodies were present in the cytoplasm of corneocytes suggesting blockade of Lamellar Body secretion. At the stratum granulosum–stratum corneum interface, non-Lamellar material displaced or replaced secreted Lamellar membranes, and in the stratum corneum, the number of Lamellar bilayers declined and Lamellar membrane organization was disrupted by foci of Lamellar/non-Lamellar phase separation. These studies demonstrate the presence of a permeability barrier abnormality in Sjogren–Larsson syndrome, which localizes to the stratum corneum interstices and can be attributed to abnormalities in Lamellar Body formation and secretion.
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hyaluronan cd44 interaction stimulates keratinocyte differentiation Lamellar Body formation secretion and permeability barrier homeostasis
Journal of Investigative Dermatology, 2006Co-Authors: Lilly Y W Bourguignon, Peter M Elias, D Crumrine, Mohamed Ramez, Eli Gilad, Patrick A Singleton, Kenneth R FeingoldAbstract:In this study we investigated whether hyaluronan (HA)–CD44 interaction influences epidermal structure and function. Our data show that CD44 deficiency is accompanied by reduction in HA staining in CD44 knockout (k/o) mouse skin leading to a marked thinning of epidermis versus wild-type mouse skin. A significant delay in the early barrier recovery (following acute barrier disruption) occurs in CD44 k/o versus wild-type mouse skin. To assess the basis for these alterations in CD44 k/o mouse epidermis, we determined that differentiation markers are greatly reduced in the epidermis of CD44 k/o versus wild-type mice, while conversely HA binding to CD44 triggers differentiation in cultured human keratinocytes. CD44 downregulation (using CD44 small interfering RNAs) also inhibits HA-mediated keratinocyte differentiation. Slower barrier recovery in CD44 k/o mice could be further attributed to reduced Lamellar Body formation, loss of apical polarization of LB secretion, and downregulation of cholesterol synthesis. Accordingly, HA–CD44 binding stimulates both LB formation and secretion. Together, these observations demonstrate new roles for HA–CD44 interaction in regulating both epidermal differentiation and lipid synthesis/secretion, which in turn influence permeability barrier homeostasis. HA–CD44 signaling could comprise a novel approach to treat skin disorders characterized by abnormalities in differentiation, lipid synthesis, and/or barrier function.
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basis for improved permeability barrier homeostasis induced by ppar and lxr activators liposensors stimulate lipid synthesis Lamellar Body secretion and post secretory lipid processing
Journal of Investigative Dermatology, 2006Co-Authors: Eungho Choi, Peter M Elias, Matt Schmuth, Debra Crumrine, Yoshikazu Uchida, Walter M Holleran, Kenneth R FeingoldAbstract:Previously, we demonstrated that topical applications of peroxisome proliferator-activated receptors (PPARs) and liver X receptor (LXR) activators improve permeability barrier homeostasis. We showed further that stimulation of epidermal differentiation provides one mechanism that could account for such improvement. Here, we studied the effects of these agents on the lipid matrix of the stratum corneum. Hairless mice were treated topically with activators of PPARα (WY14643), PPARδ (GW1514), PPARγ (ciglitazone), and LXR (22(R)-cholesterol or TO901317) or vehicle twice daily for 3 days. All activators significantly increased epidermal cholesterol, fatty acid, and sphingolipid synthesis, including the production of barrier-specific ceramide species. In addition, Lamellar Body (LB) formation, secretion, and post-secretory processing accelerated significantly following acute barrier disruption in PPAR/LXR-activator-treated animals. Finally, the activity of epidermal β-glucocerebrosidase, a key lipid-processing enzyme, increased in PPAR/LXR-activator-treated animals. Thus, topical PPAR and LXR activators stimulate epidermal lipid synthesis, increase LB secretion, and accelerate extracellular lipid processing, providing additional mechanisms that further account for their ability to improve epidermal permeability barrier homeostasis. Since the liposensors are activated by endogenous lipid metabolites, they may serve as unique regulators of barrier homeostasis.
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altered Lamellar Body secretion and stratum corneum membrane structure in netherton syndrome differentiation from other infantile erythrodermas and pathogenic implications
Archives of Dermatology, 1999Co-Authors: M Fartasch, Mary L Williams, Peter M EliasAbstract:Background The infant with Netherton syndrome (NS) typically displays a generalized erythroderma covered by fine, translucent scales, which can be difficult to distinguish clinically from erythrodermic psoriasis, nonbullous congenital ichthyosiform erythroderma, or other infantile erythrodermas. Some infants with NS develop progressive hypernatremic dehydration, failure to thrive, and enteropathy. Such complications can be fatal. Diagnosis is typically delayed until the appearance of a pathognomonic hair shaft anomaly, trichorrhexis invaginata (bamboo hair). To facilitate the early diagnosis of NS, we obtained biopsy specimens from 7 patients with erythrodermic NS and compared their morphologic findings to those of 3 patients with erythrodermic psoriasis and 2 with congenital ichthyosiform erythroderma. Biopsy specimens were processed for light and electron microscopy using postfixation with osmium tetroxide and ruthenium tetroxide. Observation In NS, and often in congenital ichthyosiform erythroderma and erythrodermic psoriasis, the stratum corneum layer was largely replaced by parakeratotic cells. A distinctive feature—premature secretion of Lamellar Body contents—occurred only in NS. Furthermore, Lamellar Body–derived extracellular lamellae and stratum corneum lipid membranes were separated extensively by foci of electron-dense material. Finally, transformation of Lamellar Body–derived lamellae into mature Lamellar membrane structures was disturbed in NS. Conclusions Premature Lamellar Body secretion and foci of electron-dense material in the intercellular spaces of stratum corneum, features not observed in other erythrodermic disorders, appear to be frequent and relatively specific markers for NS. These ultrastructural features could permit the early diagnosis of NS before the appearance of the hair shaft abnormality. These abnormalities could explain the impaired permeability barrier in NS, and account for hypernatremia and dehydration in infants with NS.
Fumitaka Kikkawa - One of the best experts on this subject based on the ideXlab platform.
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the impact of fertility treatment on the neonatal respiratory outcomes and amniotic Lamellar Body counts in twin pregnancies
Clinica Chimica Acta, 2018Co-Authors: Hiroyuki Tsuda, Tomomi Kotani, Yuichiro Takahashi, Shigenori Iwagaki, Akihiro Hirakawa, Tomoko Nakano, Kenji Imai, Takafumi Ushida, Fumie Kinoshita, Fumitaka KikkawaAbstract:Abstract Background To elucidate the impact of fertility treatment on neonatal respiratory outcomes and amniotic Lamellar Body counts (LBCs) in twin pregnancies. Methods One hundred ninety twin pairs, including 99 dichorionic twin (DCT) and 91 monochorionic twin (MCT) pairs were registered at our institutions. All amniotic fluid samples were obtained from each sac at cesarean section. Samples were analyzed immediately after arrival at the laboratory without centrifugation. We divided the patients into 3 groups: the no therapy group (natural conception), the induced ovulation group (with or without intrauterine insemination), and the assisted reproductive technology (ART) group (in vitro fertilization or intracytoplasmic sperm injection). Results No statistically significant associations between the fertility treatment and the rates of neonatal RDS/TTN were observed in the whole study population (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.45–2.00), DCT (OR, 0.86; 95%CI, 0.30–2.47), and MCT (OR, 1.45; 95%CI, 0.41–5.11). In addition, there was no association between the fertility treatment and neonatal RDS/TTN in the propensity score analysis of the whole study population (OR, 1.25; 95%CI, 0.57–2.74). Conclusions None of the individual types of fertility treatment had a direct impact on respiratory disorders such as RDS and TTN in twin infants.
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the rate of neonatal respiratory distress syndrome transient tachypnea in the newborn and the amniotic Lamellar Body count in twin pregnancies compared with singleton pregnancies
Clinica Chimica Acta, 2018Co-Authors: Hiroyuki Tsuda, Tomomi Kotani, Yuichiro Takahashi, Shigenori Iwagaki, Akihiro Hirakawa, Tomoko Nakano, Kenji Imai, Takafumi Ushida, Fumie Kinoshita, Fumitaka KikkawaAbstract:Abstract Background Whether or not the period of fetal lung maturity differs between twin and singleton pregnancies has not been clarified. We examined whether or not fetal lung maturity and fetal lung absorption are achieved earlier in twin fetuses than in singleton fetuses. Methods We registered 454 singleton pregnancies and 398 twin pregnancies with no congenital abnormalities affecting the respiratory function or neonatal deaths. All patients were delivered by Caesarean section without labor between 24 and 38 gestational weeks. The amniotic fluid samples were analyzed immediately without centrifugation. A multiple logistic regression analysis was performed to explore the relationship between twin pregnancy and neonatal respiratory distress syndrome and transient tachypnea of the newborn (RDS/TTN). Results The rate of RDS/TTN in infants was significantly higher and the Lamellar Body counts (LBCs) significantly lower in singleton pregnancies than that in twin pregnancies (P Conclusions We showed that twin fetuses experience more rapid lung maturation and lung fluid absorption than singleton fetuses, as confirmed by the higher LBC values in twin fetuses.
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amniotic Lamellar Body count predicting and distinguishing neonatal respiratory complications in twin pregnancies
Clinica Chimica Acta, 2015Co-Authors: Hiroyuki Tsuda, Tomomi Kotani, Seiji Sumigama, Yukio Mano, Yuichiro Takahashi, Shigenori Iwagaki, Ichiro Kawabata, Akihiro Hirakawa, Fumitaka KikkawaAbstract:Abstract Background Twin pregnancies have a higher rate of preterm births, making precise prediction of neonatal respiratory disorders essential. We herein examined the amniotic Lamellar Body count (LBC) and found it to be an accurate predictor of respiratory disorders in twin pregnancies. Methods Five hundred fourteen amniotic fluid samples, comprising 132 dichorionic twin (DCT) and 125 monochorionic twin (MCT) gestations, were obtained at cesarean section performed at 29 to 38 gestational weeks. Samples were analyzed immediately without centrifugation. Results There were 26 neonates (5.1%) with respiratory distress syndrome (RDS) and 43 (8.4%) with transient tachypnea of the newborn (TTN). The LBC in neonates with TTN (5.12 × 104/μl) was between the counts in RDS (1.26 × 104/μl) and controls (10.6 × 104/μl), which differed significantly. Twin concordance rates were significantly higher for TTN in MCT gestations than DCT gestations (p = 0.003) and delta LBC value was significantly smaller in MCT (3.15 ± 0.4 × 104/μl) than DCT (5.17 ± 0.5 × 104/μl) gestations (p = 0.003). Conclusions The amniotic LBC is useful for predicting respiratory disorders, including RDS and TTN, in twin pregnancies. The data in this study may indicate a genetic predisposition to TTN among MCTs.
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effect of placenta previa on neonatal respiratory disorders and amniotic Lamellar Body counts at 36 38 weeks of gestation
Early Human Development, 2014Co-Authors: Hiroyuki Tsuda, Tomomi Kotani, Seiji Sumigama, Yukio Mano, Masahiro Hayakawa, Yoshiaki Sato, Hiromi Hayakawa, Fumitaka KikkawaAbstract:Abstract Background Pregnancies with placenta previa are significantly associated with preterm delivery and cesarean section. Therefore particular attention should be paid to the incidence of neonatal respiratory disorders in pregnancies with placenta previa. Aims The purpose of this study is to examine the relationship between placenta previa and neonatal respiratory disorders, including respiratory distress syndrome (RDS) and transient tachypnea of the newborn (TTN), and to evaluate the impact of placenta previa on the amniotic Lamellar Body count (LBC) values. Methods We analyzed the data from 186 registered elective cesarean cases without fetal or maternal complications at 36–38 weeks of gestation. Amniotic fluid samples were analyzed immediately without centrifugation, and the LBC was measured using a platelet channel on the Sysmex XE-2100. Results RDS was present in four neonates (2.2%) and TTN in 12 neonates (6.5%). The rate of TTN was significantly higher and the LBC values were significantly lower in the placenta previa group than in the control group (P = 0.002 and P = 0.024). The adjusted odds ratio for neonatal TTN was 7.20 (95% confidence interval: 6.58–7.88) among females with placenta previa. In placenta previa, warning bleeding was a significant factor protecting against neonatal respiratory disorders (P = 0.046). Conclusions Placenta previa in itself is a risk factor for neonatal TTN. When an elective cesarean section is performed in cases with uncomplicated placenta previa, special care should be taken to monitor for neonatal TTN even at 36–38 weeks of gestation.
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amniotic Lamellar Body count and congenital diaphragmatic hernia in humans and in a rat model
Pediatric Research, 2013Co-Authors: Yuriko Watanabe, Hiroyuki Tsuda, Tomomi Kotani, Seiji Sumigama, Yukio Mano, Masahiro Hayakawa, Yoshiaki Sato, Fumitaka KikkawaAbstract:Amniotic Lamellar Body count and congenital diaphragmatic hernia in humans and in a rat model
Hiroyuki Tsuda - One of the best experts on this subject based on the ideXlab platform.
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the rate of neonatal respiratory distress syndrome transient tachypnea in the newborn and the amniotic Lamellar Body count in twin pregnancies compared with singleton pregnancies
Clinica Chimica Acta, 2018Co-Authors: Hiroyuki Tsuda, Tomomi Kotani, Yuichiro Takahashi, Shigenori Iwagaki, Akihiro Hirakawa, Tomoko Nakano, Kenji Imai, Takafumi Ushida, Fumie Kinoshita, Fumitaka KikkawaAbstract:Abstract Background Whether or not the period of fetal lung maturity differs between twin and singleton pregnancies has not been clarified. We examined whether or not fetal lung maturity and fetal lung absorption are achieved earlier in twin fetuses than in singleton fetuses. Methods We registered 454 singleton pregnancies and 398 twin pregnancies with no congenital abnormalities affecting the respiratory function or neonatal deaths. All patients were delivered by Caesarean section without labor between 24 and 38 gestational weeks. The amniotic fluid samples were analyzed immediately without centrifugation. A multiple logistic regression analysis was performed to explore the relationship between twin pregnancy and neonatal respiratory distress syndrome and transient tachypnea of the newborn (RDS/TTN). Results The rate of RDS/TTN in infants was significantly higher and the Lamellar Body counts (LBCs) significantly lower in singleton pregnancies than that in twin pregnancies (P Conclusions We showed that twin fetuses experience more rapid lung maturation and lung fluid absorption than singleton fetuses, as confirmed by the higher LBC values in twin fetuses.
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the impact of fertility treatment on the neonatal respiratory outcomes and amniotic Lamellar Body counts in twin pregnancies
Clinica Chimica Acta, 2018Co-Authors: Hiroyuki Tsuda, Tomomi Kotani, Yuichiro Takahashi, Shigenori Iwagaki, Akihiro Hirakawa, Tomoko Nakano, Kenji Imai, Takafumi Ushida, Fumie Kinoshita, Fumitaka KikkawaAbstract:Abstract Background To elucidate the impact of fertility treatment on neonatal respiratory outcomes and amniotic Lamellar Body counts (LBCs) in twin pregnancies. Methods One hundred ninety twin pairs, including 99 dichorionic twin (DCT) and 91 monochorionic twin (MCT) pairs were registered at our institutions. All amniotic fluid samples were obtained from each sac at cesarean section. Samples were analyzed immediately after arrival at the laboratory without centrifugation. We divided the patients into 3 groups: the no therapy group (natural conception), the induced ovulation group (with or without intrauterine insemination), and the assisted reproductive technology (ART) group (in vitro fertilization or intracytoplasmic sperm injection). Results No statistically significant associations between the fertility treatment and the rates of neonatal RDS/TTN were observed in the whole study population (odds ratio [OR], 0.95; 95% confidence interval [CI], 0.45–2.00), DCT (OR, 0.86; 95%CI, 0.30–2.47), and MCT (OR, 1.45; 95%CI, 0.41–5.11). In addition, there was no association between the fertility treatment and neonatal RDS/TTN in the propensity score analysis of the whole study population (OR, 1.25; 95%CI, 0.57–2.74). Conclusions None of the individual types of fertility treatment had a direct impact on respiratory disorders such as RDS and TTN in twin infants.
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risk assessment for neonatal rds ttn using gestational age and the amniotic Lamellar Body count in twin pregnancies
Clinica Chimica Acta, 2015Co-Authors: Hiroyuki Tsuda, Tomomi Kotani, Seiji Sumigama, Yukio Mano, Yuichiro Takahashi, Ichiro Kawabata, Akihiro Hirakawa, Tomoko Nakano, Kenji Imai, Shigenori IwagakiAbstract:Abstract Background The amniotic Lamellar Body count (LBC) is useful for predicting respiratory distress syndrome (RDS) and transient tachypnea of the newborn (TTN) in twin pregnancies. However, the risk of neonatal respiratory complications varies with gestational age (GA). We herein created a model to predict the risk for RDS and TTN using GA and the LBC in twin pregnancies. Methods Six hundred thirty-two amniotic fluid samples, comprising 169 dichorionic twin (DCT) and 147 monochorionic twin (MCT) gestations, were obtained at Cesarean section. The samples were analyzed immediately without centrifugation. A logistic regression model including the LBC and GA was used to develop the prediction model for RDS/TTN. Results There were 101 neonates (16.0%) with RDS/TTN. The GA and LBC were significant independent factors affecting RDS/TTN. According to the logistic regression model, we determined the probability of RDS/TTN given the values of GA and the LBC. The overall diagnostic accuracy for predicting neonatal RDS/TTN using GA and the LBC was higher than the use of the LBC alone. Conclusions GA-specific LBC cutoffs for the risk assessment of neonatal RDS/TTN have been considered to be more accurate in twin pregnancies. Our findings provide valuable, new information for the management of twin pregnancies.
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amniotic Lamellar Body count predicting and distinguishing neonatal respiratory complications in twin pregnancies
Clinica Chimica Acta, 2015Co-Authors: Hiroyuki Tsuda, Tomomi Kotani, Seiji Sumigama, Yukio Mano, Yuichiro Takahashi, Shigenori Iwagaki, Ichiro Kawabata, Akihiro Hirakawa, Fumitaka KikkawaAbstract:Abstract Background Twin pregnancies have a higher rate of preterm births, making precise prediction of neonatal respiratory disorders essential. We herein examined the amniotic Lamellar Body count (LBC) and found it to be an accurate predictor of respiratory disorders in twin pregnancies. Methods Five hundred fourteen amniotic fluid samples, comprising 132 dichorionic twin (DCT) and 125 monochorionic twin (MCT) gestations, were obtained at cesarean section performed at 29 to 38 gestational weeks. Samples were analyzed immediately without centrifugation. Results There were 26 neonates (5.1%) with respiratory distress syndrome (RDS) and 43 (8.4%) with transient tachypnea of the newborn (TTN). The LBC in neonates with TTN (5.12 × 104/μl) was between the counts in RDS (1.26 × 104/μl) and controls (10.6 × 104/μl), which differed significantly. Twin concordance rates were significantly higher for TTN in MCT gestations than DCT gestations (p = 0.003) and delta LBC value was significantly smaller in MCT (3.15 ± 0.4 × 104/μl) than DCT (5.17 ± 0.5 × 104/μl) gestations (p = 0.003). Conclusions The amniotic LBC is useful for predicting respiratory disorders, including RDS and TTN, in twin pregnancies. The data in this study may indicate a genetic predisposition to TTN among MCTs.
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effect of placenta previa on neonatal respiratory disorders and amniotic Lamellar Body counts at 36 38 weeks of gestation
Early Human Development, 2014Co-Authors: Hiroyuki Tsuda, Tomomi Kotani, Seiji Sumigama, Yukio Mano, Masahiro Hayakawa, Yoshiaki Sato, Hiromi Hayakawa, Fumitaka KikkawaAbstract:Abstract Background Pregnancies with placenta previa are significantly associated with preterm delivery and cesarean section. Therefore particular attention should be paid to the incidence of neonatal respiratory disorders in pregnancies with placenta previa. Aims The purpose of this study is to examine the relationship between placenta previa and neonatal respiratory disorders, including respiratory distress syndrome (RDS) and transient tachypnea of the newborn (TTN), and to evaluate the impact of placenta previa on the amniotic Lamellar Body count (LBC) values. Methods We analyzed the data from 186 registered elective cesarean cases without fetal or maternal complications at 36–38 weeks of gestation. Amniotic fluid samples were analyzed immediately without centrifugation, and the LBC was measured using a platelet channel on the Sysmex XE-2100. Results RDS was present in four neonates (2.2%) and TTN in 12 neonates (6.5%). The rate of TTN was significantly higher and the LBC values were significantly lower in the placenta previa group than in the control group (P = 0.002 and P = 0.024). The adjusted odds ratio for neonatal TTN was 7.20 (95% confidence interval: 6.58–7.88) among females with placenta previa. In placenta previa, warning bleeding was a significant factor protecting against neonatal respiratory disorders (P = 0.046). Conclusions Placenta previa in itself is a risk factor for neonatal TTN. When an elective cesarean section is performed in cases with uncomplicated placenta previa, special care should be taken to monitor for neonatal TTN even at 36–38 weeks of gestation.
Kenneth R Feingold - One of the best experts on this subject based on the ideXlab platform.
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hyaluronan cd44 interaction stimulates keratinocyte differentiation Lamellar Body formation secretion and permeability barrier homeostasis
Journal of Investigative Dermatology, 2006Co-Authors: Lilly Y W Bourguignon, Peter M Elias, D Crumrine, Mohamed Ramez, Eli Gilad, Patrick A Singleton, Kenneth R FeingoldAbstract:In this study we investigated whether hyaluronan (HA)–CD44 interaction influences epidermal structure and function. Our data show that CD44 deficiency is accompanied by reduction in HA staining in CD44 knockout (k/o) mouse skin leading to a marked thinning of epidermis versus wild-type mouse skin. A significant delay in the early barrier recovery (following acute barrier disruption) occurs in CD44 k/o versus wild-type mouse skin. To assess the basis for these alterations in CD44 k/o mouse epidermis, we determined that differentiation markers are greatly reduced in the epidermis of CD44 k/o versus wild-type mice, while conversely HA binding to CD44 triggers differentiation in cultured human keratinocytes. CD44 downregulation (using CD44 small interfering RNAs) also inhibits HA-mediated keratinocyte differentiation. Slower barrier recovery in CD44 k/o mice could be further attributed to reduced Lamellar Body formation, loss of apical polarization of LB secretion, and downregulation of cholesterol synthesis. Accordingly, HA–CD44 binding stimulates both LB formation and secretion. Together, these observations demonstrate new roles for HA–CD44 interaction in regulating both epidermal differentiation and lipid synthesis/secretion, which in turn influence permeability barrier homeostasis. HA–CD44 signaling could comprise a novel approach to treat skin disorders characterized by abnormalities in differentiation, lipid synthesis, and/or barrier function.
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basis for improved permeability barrier homeostasis induced by ppar and lxr activators liposensors stimulate lipid synthesis Lamellar Body secretion and post secretory lipid processing
Journal of Investigative Dermatology, 2006Co-Authors: Eungho Choi, Peter M Elias, Matt Schmuth, Debra Crumrine, Yoshikazu Uchida, Walter M Holleran, Kenneth R FeingoldAbstract:Previously, we demonstrated that topical applications of peroxisome proliferator-activated receptors (PPARs) and liver X receptor (LXR) activators improve permeability barrier homeostasis. We showed further that stimulation of epidermal differentiation provides one mechanism that could account for such improvement. Here, we studied the effects of these agents on the lipid matrix of the stratum corneum. Hairless mice were treated topically with activators of PPARα (WY14643), PPARδ (GW1514), PPARγ (ciglitazone), and LXR (22(R)-cholesterol or TO901317) or vehicle twice daily for 3 days. All activators significantly increased epidermal cholesterol, fatty acid, and sphingolipid synthesis, including the production of barrier-specific ceramide species. In addition, Lamellar Body (LB) formation, secretion, and post-secretory processing accelerated significantly following acute barrier disruption in PPAR/LXR-activator-treated animals. Finally, the activity of epidermal β-glucocerebrosidase, a key lipid-processing enzyme, increased in PPAR/LXR-activator-treated animals. Thus, topical PPAR and LXR activators stimulate epidermal lipid synthesis, increase LB secretion, and accelerate extracellular lipid processing, providing additional mechanisms that further account for their ability to improve epidermal permeability barrier homeostasis. Since the liposensors are activated by endogenous lipid metabolites, they may serve as unique regulators of barrier homeostasis.
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selective obliteration of the epidermal calcium gradient leads to enhanced Lamellar Body secretion
Journal of Investigative Dermatology, 1994Co-Authors: Gopinathan K Menon, Peter M Elias, Lisa F Price, Bommi Bommannan, Kenneth R FeingoldAbstract:Abstract The epidermal permeability barrier is formed by lipids delivered to the intercellular spaces through the secretion of Lamellar bodies. Prior studies have shown that the rate of Lamellar Body secretion appears to be regulated by the extracellular calcium content of the upper epidermis, which is altered following permeability barrier disruption. To determine directly whether changes in extracellular calcium content in the upper epidermis versus disruption of the barrier regulate Lamellar Body secretion, we experimentally manipulated the Ca ++ content of the upper epidermis by sonophoresis of aqueous solutions containing physiologic Ca ++ (and K + ) versus ion-free solutions across hairless mouse stratum corneum. Sonophoresis at 15 MHz did not alter barrier function, but in the absence of Ca ++ the extracellular calcium content of the outer epidermis, as revealed by ion capture cytochemistry, was displaced downward toward the basal layer and dermis. In contrast, following sonophoresis of Ca ++ -containing solutions, the extracellular Ca ++ gradient became obscured by excess Ca ++ in the cytosol at all levels of the epidermis. These changes in the extracellular calcium content lead, in turn, to accelerated Lamellar Body secretion (with low Ca ++ ), or basal rates of Lamellar Body secretion (with normal Ca ++ ). These results demonstrate that the epidermal extracellular calcium content in the upper epidermis can be manipulated by sonophoresis without prior barrier disruption, and that changes in the Ca ++ gradient induce Lamellar Body secretion, independent of barrier disruption.
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Lamellar Body secretory response to barrier disruption
Journal of Investigative Dermatology, 1992Co-Authors: Gopinathan K Menon, Kenneth R Feingold, Peter M EliasAbstract:Abundant evidence points to an important role for epidermal Lamellar Body secretion in permeability barrier maintenance, However, the response of the Lamellar Body secretory system to barrier disruption has not been examined. Hence, we examined amined the Lamellar Body secretory response at various points after acetone induced barrier abrogation in hairless mice in air exposed animals and those occluded with impermeable versus vapor permeable membranes, Tape stripped animals served as a control for chemical toxicity. Barrier perturbation with either acetone or tape stripping was followed by rapid secretion of Lamellar Body contents from the uppermost granular cell layer, leaving the cytosol largely devoid of Lamellar bodies. The newly secreted Lamellar Body contents comprised pleated sheets (not “discs,” as previously thought), which unfurled in the intercellular spaces at the granular cornified cell interface. At this time (15-30 min) the basic unit structure of the Lamellar bilayers in the mid to upper stratum corneum appeared disorganized an interspersed with large lacunae reflection solvent extraction Nascent Lamellar bodies began to reappear in the granular cell cytosol by 30 min and by 360 min, the cells displayed a full complement of normal appearing Lamellar bodies. Between 60 and 360 min, the density of Lamellar Body sheets at the granular cornified cell interface increased, whereas the membrane bilayer of the outer stratum corneum remained disorganized. New Lamellar bilayer units first appeared in the lower stratum corneum between 60 and 180 min, as a result of the transformation of secreted Lamellar Body sheets and over time these lamellae appeared at more apical locations. Occlusion with a water vapor – impermeable but not a vapor-permeable membrane resulted in a) decreased quantities of Lamellar bodies and Lamellar Body – derived intercellular products; b) formation of Lamellar bodies with abnormal internal contents; c) inhibition of Lamellar Body secretion; and d)inhibition of transformation of Lamellar Body – derived sheets into Lamellar bilayer units. These results demonstrate the central role of the Lamellar Body – secretory system in barrier repair and homeostasis.
Ann M Gronowski - One of the best experts on this subject based on the ideXlab platform.
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predicting respiratory distress syndrome using gestational age and Lamellar Body count
Clinical Biochemistry, 2013Co-Authors: Qiuhong Zhao, David G Grenache, Zhen Zhao, Van Leungpineda, Carmen L Wiley, Paul J Nelson, Fred S Apple, Amy K Saenger, Ann M GronowskiAbstract:Abstract Objectives To design a predictive model for assessing the risk of developing respiratory distress syndrome (RDS) using gestational age (GA) and Lamellar Body counts (LBC). Design and methods LBCs and patient outcome data was obtained from five medical centers. A total of 223 patients were included in this study; 19 gave birth to infants that developed RDS, 204 gave birth to infants that were unaffected. The absolute risk and odds ratios of an infant developing RDS as a function of GA and LBC were calculated. Logistic analysis was used to model the odds of RDS as a function of GA and LBC. Results The odds of RDS decreased for each increasing week of GA and decreased with increase in the LBC. GA-specific LBC cutoffs are provided for sensitivities between 84 and 100%. The bias adjusted area under the ROC curve for the classification of RDS, based on GA and LBC, was 0.906 using the logistic model and 0.746 using a single cutoff of LBC (50,000/μL) to classify immaturity. Conclusions GA-specific risk assessment and GA-specific cutoffs provide increased sensitivity and specificity in the evaluation of fetal lung maturity.
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validation of Lamellar Body counts using three hematology analyzers
American Journal of Clinical Pathology, 2010Co-Authors: Christina M Lockwood, Chance J Crompton, Joan K Riley, Keith Landeros, Dennis J Dietzen, David G Grenache, Ann M GronowskiAbstract:The Lamellar Body count (LBC) represents an alternative method to the TDx-FLM II (Abbott Laboratories, Abbott Park, IL), which is planned to be discontinued, for assessing fetal lung maturity. Our objective was to validate the LBC on 3 hematology analyzers (Coulter LH 750 and Coulter Ac·T diff2, Beckman Coulter, Brea, CA; and Sysmex XE-2100, Sysmex, Mundelein, IL) to serve as a template, for other laboratories attempting to perform in-house validation. Intra-assay and interassay coefficients of variation ranged from 1. 7% to 21.8% and 1.9% to 7.1%, respectively, and all analyzers demonstrated excellent linearity. Whole blood and meconium were shown to interfere with LBCs, and specimens with these contaminants should be tested using phosphatidyl glycerol. With a TDx-FLM II cutoff of 55 mg/g or more and an LBC cutoff of 50,000/μL or more for maturity, concordance between the TDx-FLM II and the LBC on all instruments was poor (<80% in all cases). Concordance between hematology analyzers was excellent (≥94%). When laboratories are performing in-house validations, they should not correlate LBC with TDx-FLM II results without outcome data. Correlation with another validated LBC method is preferred.
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Lamellar Body counts performed on automated hematology analyzers to assess fetal lung maturity
Labmedicine, 2008Co-Authors: Ji Lu, Ann M GronowskiAbstract:Laboratory assessment of fetal lung maturity assists obstetricians in estimating the risk of respiratory distress syndrome (RDS) when premature delivery of an infant is being considered. The status of fetal lung maturity is reflected in the concentrations of specific phospholipids and the number of surfactant-containing particles, or Lamellar bodies, in amniotic fluid. Since Lamellar Body volumes are similar to platelets, automated hematology analyzers can provide rapid and precise Lamellar Body counts (LBCs). However, hematology analyzer manufacturers use different methods to enumerate platelets, leading to a lack of concordance between instrument brands when counting Lamellar bodies. Laboratories performing LBCs should be aware of this important analytical variable when providing interpretations of LBC results.
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a direct comparison between Lamellar Body counts and fluorescent polarization methods for predicting respiratory distress syndrome
American Journal of Clinical Pathology, 2006Co-Authors: Shannon Haymond, Veronica Luzzi, Curtis A Parvin, Ann M GronowskiAbstract:Our objective was to directly compare the diagnostic usefulness of Lamellar Body counting (LBC) and the TDx-FLM II assay (Abbott Laboratories, Abbott Park, IL) for predicting respiratory distress syndrome (RDS). This was a 5-year, retrospective, cohort study. A diagnosis of RDS was given to infants who received surfactant treatment and/or required ventilator support and/or continuous positive airway pressure for more than 24 hours. There were 172 infants without RDS and 12 with RDS included in the study. By using a TDx-FLM II cutoff of 55 mg/g or more for maturity, the sensitivity was 83%, specificity was 65%, predictive value of a mature result was 98%, and predictive value of an immature result was 14%. These results were similar to LBC using a cutoff of 50,000/μL or more with sensitivity of 92%, a specificity of 60%, a predictive value of a mature result of 99%, and a predictive value of an immature result of 14%. The LBC and TDx-FLM II methods have similar clinical usefulness.
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Lamellar Body count in amniotic fluid a comparative study of four different hematology analyzers
Clinical Chemistry, 2003Co-Authors: Arpad Szallasi, Ann M GronowskiAbstract:The accurate antenatal prediction of fetal lung maturity (FLM) based on results from amniotic fluid samples is of utmost importance in the prevention of neonatal respiratory distress syndrome and its complications. The current “gold standard” for the determination of FLM is the evaluation of phospholipids (i.e., measurement of lecithin/sphingomyelin ratio and quantification of phosphatidylglycerol) in amniotic fluid samples by thin-layer chromatography. These tests are, however, time-consuming and not continuously available at most institutions. Lamellar bodies are lamellated phospholipids that represent a storage form of surfactant (1). Because Lamellar Body diameter (range, 1–5 μm) is similar to that of small platelets, Lamellar Body counts (LBCs) can be obtained rapidly with use of the platelet channel of a hematology analyzer (2). Recently, a consensus LBC protocol was published, and a FLM cutoff of 50 000/μL was suggested without discussion regarding the hematology analyzer used (3). The majority of published reports to date have used a Coulter brand of hematology analyzer to establish clinical decision limits (2)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13). The published experience with other hematology analyzers, such as the Sysmex NE-1500 (14), for obtaining LBCs is limited. One study used LBCs from three different analyzers (two from Coulter, one from Sysmex) to assess FLM without providing any evidence that the instrumentation was not a source of imprecision (9). Our objective was therefore to compare LBC concordance from the following four hematology analyzers: Coulter Gen-S (Beckman Coulter), Sysmex XE-2100 (Sysmex), Cell-dyn 3500 (Abbott Laboratories), and ADVIA 120 (Bayer Corporation). Leftover amniotic fluid samples sent to the Barnes-Jewish …
