scholarly journals Further placental pathology in mild COVID-19 of term pregnancy with pathophysiological correlates

2020 ◽  
Author(s):  
Anastasia E. Konstantinidou ◽  
Vassiliki Papaevangelou ◽  
Athanasios Tsakris ◽  
Nikolaos E. Spanakis ◽  
Garyfallia Syridou ◽  
...  
Keyword(s):  
Thrombus Formation ◽  
Neonatal Morbidity ◽  
Low Grade ◽  
Placental Pathology ◽  
Vascular Changes ◽  
Rt Pcr ◽  
Term Pregnancy ◽  
Febrile Response ◽  
Intervillous Space ◽  
Systemic Nature

Abstract Placental pathology related to SARS-COV-2 infection during pregnancy is under investigation, with emerging but still limited and variable data, mainly including changes of fetal and maternal vascular malperfusion. We observed novel pathological findings not previously reported in two term placentas delivered from women mildly affected with COVID-19, with a 2-day and 6-day interval between the onset of symptoms and delivery. The main changes involved the maternal more than the fetal components of the placenta and included a tendency toward thrombosis and fibrin formation, and mild maternal malperfusion. We further observed fibrin degeneration in the intervillous space, the presence of particles of undetermined origin, and mild or moderate maternal decidual inflammatory exudates consisting of monocytes, macrophages, T-lymphocytes, and plasmacytes. Mild inflammation and incipient mural thrombus formation were noted in the fetal vasculature, as well as endothelial vacuolation of the umbilical vessels, not previously described. The maternal changes were more prominent in the case with a relatively longer clinical manifestation-to-delivery interval, and were associated to a prolonged postpartum maternal viral carriage of 30 days and the development of a low-grade febrile response in the neonate. Both infants showed mild morbidity but eventually had a very good outcome. RT-PCR was negative for SARS-CoV-2 RNA in both cases.We concluded that placental involvement in mild COVID-19 of very short duration at term pregnancy suggested the systemic nature of the disease and appeared related to, though not pathognomonic of COVID-19. Fetoplacental vascular changes and endothelial vacuolation associated with mild neonatal morbidity may suggest a possible transplacental impact on the fetus, to be further investigated.

scholarly journals Analysis of placental pathology and fetal outcome

2018 ◽  
Vol 7 (4) ◽  
pp. 1322
Author(s):  
Amrutha Ramachandran
Keyword(s):  
Vessel Wall ◽  
Perinatal Death ◽  
Neonatal Morbidity ◽  
Fetal Outcome ◽  
Careful Examination ◽  
Wall Thickening ◽  
P Value ◽  
Placental Pathology ◽  
Exact Test ◽  
Tertiary Teaching

Background: A careful examination of placenta along with microscopic study may frequently point to the cause of perinatal death. The American College of Pathologists has provided guidelines for the examination of placenta. Aim of this study was to illustrate the gross and histopathological changes in placenta in certain normal and abnormal pregnancies and to analyse the relationship of placental pathology with fetal outcome.Methods: A prospective study of 120 deliveries at a tertiary teaching centre in India. Each placenta was studied macroscopically and sent to the pathology department for histological examination.  The study included placentas of normal pregnancies and those with maternal high-risk features. The placenta was fixed in formalin and 6 sections were taken. The paraffin sections were studied for vessel wall thickening, infarction, villitis, chorioangiosis, calcification and intervillous hemorrhage. The primary outcome variables were fetal and neonatal morbidity. Abnormal fetal /neonatal events in each histological group were compared with the normal group using Ψ2 test for homogeneity. For cell frequencies less than 5, Fischer exact test was used.Results: Vessel wall thickening was demonstrated in 54/120 patients (45%). 7 out of 54 (12.96%) fetuses were still born in this group compared to 2/30 (6.67%) with normal histology (p value <0.05). Infarcts were demonstrated in 15/120 (12.5%). The occurrence of abnormal neonatal events in this group was significant p <0.01.Conclusions: Placental histological features of vessel wall thickening, and infarction is associated with abnormal fetal and neonatal outcome. Larger studies are required to establish the inference.

Novel Fusion of the MALT1/MLT and MAP4 Genes Detected in a Diffuse Large B-Cell Lymphoma.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2838-2838
Author(s):  
Eva M. Murga Penas ◽  
Kristina Hinz ◽  
Petra Behrmann ◽  
Martin L. Hansmann ◽  
Claudia Becher ◽  
...  
Keyword(s):  
B Cell ◽  
B Cell Lymphoma ◽  
Low Grade ◽  
Rt Pcr ◽  
B Cell Lymphomas ◽  
Specific Primers ◽  
Interphase Fish ◽  
Exon 9 ◽  
Race Pcr ◽  
Large B Cell

Abstract The MALT1/MLT gene codes for a human paracaspase and plays a crucial role in NF-κB activation in response to TCR induction. Rearrangements of MALT1/MLT by the translocations t(11;18)(q21;q21) and t(14;18)(q32;q21) act by activating the NF-κB pathway and are the most frequent structural chromosomal abnormalities in extranodal marginal zone B-cell lymphomas of the MALT-type. They occur in 20 to 50% of low grade MALT lymphomas, but with only rare exception are absent in diffuse large B-cell lymphomas (DLBCL). By screening 118 diffuse large B-cell lymphomas and 28 Burkitt’s lymphomas by interphase FISH with probes flanking MALT1/MLT (Abbott Vysis), we found two cases with a break within MALT1/MLT. Further experiments with plasmid subclones from the BAMH1 fragments of PAC 152M5, which spans the entire coding region of MALT1/MLT, confirmed the break within MALT1/MLT in one case. This patient presented with a relapse of a DLBCL, centroblastic subtype, without any concomitant low-grade component or lymphoepithelial lesions. During relapse only nodal manifestations were seen (stage IIIA), however, at the time of primary diagnosis a lymphoma infiltration of one adrenal gland was present. FISH experiments with MALT1/MLT, API2 and IGH specific probes did not identify a t(11;18) or a t(14;18). 3′ RACE-PCR revealed a novel in frame fusion of exon 9 of the MALT1/MLT gene and exon 9 of the microtubule-associated protein 4 (MAP4) gene. RT-PCR with specific primers for MALT1/MLT and MAP4 confirmed the presence of the fusion transcript MALT1/MLT-MAP4. In addition, interphase FISH showed that the translocation was accompanied by a deletion of MALT1/MLT sequences distal to the breakpoint including the caspase-like domain, which is essential for activation of the NF-κB pathway in MALT lymphomas. Corresponding to this result, 5′ RACE-PCR with specific primers for MALT1/MLT and RT-PCR with nested primers for MAP4 and MALT1/MLT did not detect the reciprocal 5′MAP4-3′MALT1/MLT transcript. The MAP4 gene on chromosome 3p21 is the major microtubule-associated protein in non-neuronal tissues and promotes microtubule polymerization. Disruption of the microtubule-dynamics is induced by microtubule-interfering drugs, such as taxanes and Vinca alkaloids. We conclude that the 5′MALT1/MLT-3′MAP4 fusion is the pathogenetically relevant transcript in this non-reciprocal der(18)t(3;18)(p21;q21) translocation. The absence of the caspase like domain distinguishes this novel gene fusion, MALT1/MLT-MAP4, from the API2-MALT1/MLT in the t(11;18) and the IGH-MALT1/MLT in the t(14;18), in which the caspase like domain is invariably present and points to MAP4 as a new target gene with possible therapeutic implications in DLBCL.

Abnormal Expression of TRAF Adapter Proteins in Waldenstrom’s Macroglobulinemia.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4640-4640
Author(s):  
Xavier Leleu ◽  
Lian Xu ◽  
Zachary R. Hunter ◽  
Anne-Sophie Moreau ◽  
Xiaoying Jia ◽  
...  
Keyword(s):  
Western Blot ◽  
Cell Lines ◽  
Blot Analysis ◽  
Western Blot Analysis ◽  
Low Grade ◽  
Adapter Proteins ◽  
Rt Pcr ◽  
Growth And Survival ◽  
Healthy Donors ◽  
Sirna Knockdown

Abstract Background: Waldenström’s Macroglobulinemia (WM) is an incurable low-grade lymphoplasmacytic lymphoma with as yet unknown genetic basis for its pathogenesis. Several TNF family members (CD40L, APRIL and BAFF/BLYS) are known to regulate WM growth and survival. TRAFs are a novel family of adapter proteins that facilitate pro-apoptotic (TACI) or pro-survival/differentiation (CD40, BAFFR, BCMA) receptor signaling mediated by TNF family ligands. Therefore, understanding the TRAF system in WM may yield important clues about WM growth and survival. Methods: WM cell lines (BCWM.1 and WSU-WM), IgM secreting low-grade lymphoma cell lines (MEK1, RL, Namalwa), and primary bone marrow CD19+ selected lymphoplasmacytic cells (LPC) from 20 WM patients and 6 healthy donors were evaluated for TRAF (TRAF 2, 3, 5, 6) expression using semi quantitative RT-PCR and/or western blot analysis. Results: The TNF familiy receptors CD40, BAFFR, BCMA, and TACI were expressed in all cell lines tested as well as in CD19+ selected LPC from WM patients and healthy donors. Moreover, TRAF 2, 3, 5, 6 were expressed in all cell lines by both RT-PCR and western blot analysis. In contrast, we observed loss or abnormally low expression of both TRAF 2 and 5 in 6/20 (30%) patients, whilst TRAF 3 was absent or abnormally low in 3/30 (15%) patients. TRAF 6 was expressed in all patients. Among healthy donors, we observed expression of all TRAF adapter proteins. Conclusion: Up to one third of WM patients demonstrate loss of TRAF 2 and 5 adapter proteins which facilitate signaling through the pro-apoptotic receptor TACI. Ongoing studies including gene sequencing and siRNA knockdown models are delineating a role for TRAF loss in the pathogenesis of WM.

scholarly journals Retrospective observational RT-PCR analyses on 688 babies born to 843 SARS-CoV-2 positive mothers, placental analyses and diagnostic analyses limitations suggest vertical transmission is possible.

2021 ◽  
Vol 13 (1) ◽  
pp. 53-66 ◽  
Author(s):  
G. Bahadur ◽  
M. Bhat ◽  
S. Acharya ◽  
D. Janga ◽  
B. Campbell ◽  
...  
Keyword(s):  
Vertical Transmission ◽  
Research Question ◽  
Diagnostic Testing ◽  
Placental Pathology ◽  
Rt Pcr ◽  
Chain Reaction ◽  
Serial Testing ◽  
Medical Termination ◽  
Polymerase Chain ◽  
Positive Results

Research question: Is there vertical transmission (from mother to baby antenatally or intrapartum) after SARS-CoV-2 (COVID-19) infected pregnancy? Study design: A systematic search related to SARS-CoV-2 (COVID-19), pregnancy, neonatal complications, viral and vertical transmission. The duration was from December 2019 to May 2020. Results: A total of 84 studies with 862 COVID positive women were included. Two studies had ongoing pregnancies while 82 studies included 705 babies, 1 miscarriage and 1 medical termination of pregnancy (MTOP). Most publications (50/84, 59.5%), reported small numbers (<5) of positive babies. From 75 studies, 18 babies were COVID-19 positive. The first reverse transcription polymerase chain reaction (RT-PCR) diagnostic test was done in 449 babies and 2 losses, 2nd RT-PCR was done in 82 babies, IgM tests were done in 28 babies, and IgG tests were done in 28 babies. On the first RT-PCR, 47 studies reported time of testing while 28 studies did not. Positive results in the first RT-PCR were seen in 14 babies. Earliest tested at birth and the average time of the result was 22 hours. Three babies with negative first RT-PCR became positive on the second RT-PCR at day 6, day 7 and at 24 hours which continued to be positive at 1 week. Four studies with a total of 4 placental swabs were positive demonstrating SARS-CoV-2 localised in the placenta. In 2 studies, 10 tests for amniotic fluid were positive for SARS-CoV-2. These 2 babies were found to be positive on RT-PCR on serial testing. Conclusion: Diagnostic testing combined with incubation period and placental pathology indicate a strong likelihood that intrapartum vertical transmission of SARS-CoV-2 (COVID-19) from mother to baby is possible.

scholarly journals The IgG Antibody Paradox in Insulin Resistance: Pathogenic and Therapeutic

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A443-A443
Author(s):  
Andrew Lipchik ◽  
Sooyeon Lee ◽  
Justin P Annes ◽  
Michael P Snyder
Keyword(s):  
Insulin Resistance ◽  
Insulin Sensitivity ◽  
Diabetic Mouse ◽  
High Dose ◽  
Low Grade ◽  
Igg Antibody ◽  
Glucose Levels ◽  
Insulin Dependent ◽  
High Doses ◽  
Systemic Nature

Abstract Chronic low-grade inflammation and mitochondrial dysfunction are hallmarks of insulin resistance. However, the mechanisms by which the immune system can propagate systemic insulin resistance remains poorly understood. IgG antibodies are a critical component of immunity and display paradoxical properties. IgG can propagate inflammation by crosslinking Fc receptors activating innate immune cells, and conversely, when given intravenously at high doses (1–2 g/kg intravenous immunoglobulin), actively suppress inflammation. Here, we demonstrate that IgG can exert similar paradoxical properties on glucose metabolism. IgG can elicit insulin resistance, and conversely, when given at high doses, promote insulin sensitivity in a diabetic mouse model. IgG, through its Fc-mediated interactions, suppresses insulin-induced mitochondrial function as well as insulin signaling. Modulation of insulin-dependent mitochondrial respiration by serum or purified IgG highly correlates (R2 = 0.70) with the quantitative measurement of insulin sensitivity accessed by the modified insulin suppression test. Our studies indicate that IgG antibody glycosylation is critically important to these conflicting actions. In mice and humans, the progression of insulin resistance is associated with reduced IgG Fc region sialylation, and administration of asialylated IgG is sufficient to cause insulin resistance in IgG null mice. On the other hand, a single administration of high-dose IgG significantly improved insulin and glucose tolerance as well as plasma glucose levels lasting over 72 days post-administration. These results demonstrate new insights into the systemic nature of insulin resistance, a novel mechanism of the disease, and an innovative therapeutic strategy for treating type 2 diabetes.

scholarly journals Prostaglandin E2-synthesizing enzymes in fever: differential transcriptional regulation

2002 ◽  
Vol 283 (5) ◽  
pp. R1104-R1117 ◽  
Author(s):  
Andrei I. Ivanov ◽  
Ralph S. Pero ◽  
Adrienne C. Scheck ◽  
Andrej A. Romanovsky
Keyword(s):  
De Novo ◽  
Phase Iii ◽  
Rt Pcr ◽  
Febrile Response ◽  
Major Mechanism ◽  
High Magnitude ◽  
Cox 2 ◽  
Wistar Kyoto ◽  
The Brain ◽  
Cox 1

The febrile response to lipopolysaccharide (LPS) consists of three phases ( phases I–III), all requiring de novo synthesis of prostaglandin (PG) E2. The major mechanism for activation of PGE2-synthesizing enzymes is transcriptional upregulation. The triphasic febrile response of Wistar-Kyoto rats to intravenous LPS (50 μg/kg) was studied. Using real-time RT-PCR, the expression of seven PGE2-synthesizing enzymes in the LPS-processing organs (liver and lungs) and the brain “febrigenic center” (hypothalamus) was quantified. Phase I involved transcriptional upregulation of the functionally coupled cyclooxygenase (COX)-2 and microsomal (m) PGE synthase (PGES) in the liver and lungs. Phase II entailed robust upregulation of all enzymes of the major inflammatory pathway, i.e., secretory (s) phospholipase (PL) A2-IIA → COX-2 → mPGES, in both the periphery and brain. Phase III was accompanied by the induction of cytosolic (c) PLA2-α in the hypothalamus, further upregulation of sPLA2-IIA and mPGES in the hypothalamus and liver, and a decrease in the expression of COX-1 and COX-2 in all tissues studied. Neither sPLA2-V nor cPGES was induced by LPS. The high magnitude of upregulation of mPGES and sPLA2-IIA (1,257-fold and 133-fold, respectively) makes these enzymes attractive targets for anti-inflammatory therapy.

Copeptin in Preeclampsia Development

2019 ◽  
Vol 15 (3) ◽  
pp. 159-164
Author(s):  
Nalini Govender ◽  
Jagidesa Moodley ◽  
Thajasvarie Naicker
Keyword(s):  
Blood Pressure ◽  
Early Diagnosis ◽  
Arginine Vasopressin ◽  
Neonatal Morbidity ◽  
Risk Indicator ◽  
Clinical Use ◽  
Stable Component ◽  
Clinical Support ◽  
Systemic Nature ◽  
Circulating Levels

Background: Preeclampsia complicates 2-8% of all pregnancies worldwide and is one of the leading causes of maternal and neonatal morbidity and mortality. It occurs after the 20th week of gestation and is characterized by high blood pressure, proteinuria or end-organ disease. The heterogeneous and multi-systemic nature of this disease has led to the elusive pathophysiology which delays timely diagnoses and the clinical treatment of those affected. Objective: Despite the extensive investigations surrounding the inclusion of various potential markers for PE prediction, early diagnosis remains unresolved. Quantification of copeptin, a stable component of the arginine vasopressin (AVP) precursor is shown to be relatively reliable in confirming the circulating levels of AVP. Conclusion: Elevated copeptin levels confirmed in pregnant women have also provided clinical support for its role in PE development. However, its clinical use in predicting disease severity in early-onset pre-eclampsia has been debatable. This review thus recapitulates the current literature surrounding copeptin and its potential as a risk indicator for PE development.</P>

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