Placental T2* and BOLD effect in response to hyperoxia in normal and growth-restricted pregnancies: multicenter cohort study.

OBJECTIVES: Blood-oxygen-level-dependent (BOLD) magnetic resonance imaging (MRI) facilitates the non-invasive in-vivo evaluation of placental oxygenation. The aims of this study were to identify and quantify a relative BOLD effect in response to hyperoxia in the human placenta and to compare it between pregnancies with and those without fetal growth restriction (FGR). METHODS: This was a prospective multicenter study (NCT02238301) of 19 pregnancies with FGR (estimated fetal weight (EFW) on ultrasound < 5th centile) and 75 non-FGR pregnancies (controls) recruited at two centers in Paris, France. Using a 1.5-Tesla MRI system, the same multi-echo gradient-recalled echo (GRE) sequences were performed at both centers to obtain placental T2* values at baseline and in hyperoxic conditions. The relative BOLD effect was calculated according to the equation 100 × (hyperoxic T2* - baseline T2*)/baseline T2*. Baseline T2* values and relative BOLD effect were compared according to EFW (FGR vs non-FGR), presence/absence of Doppler anomalies and birth weight (small-for-gestational age (SGA) vs non-SGA). RESULTS: We observed a relative BOLD effect in response to hyperoxia in the human placenta (median, 33.8% (interquartile range (IQR), 22.5-48.0%)). The relative BOLD effect did not differ significantly between pregnancies with and those without FGR (median, 34.4% (IQR, 24.1-48.5%) vs 33.7% (22.7-47.4%); P = 0.95). Baseline T2* Z-score adjusted for gestational age at MRI was significantly lower in FGR pregnancies compared with non-FGR pregnancies (median, -1.27 (IQR, -4.87 to -0.10) vs 0.33 (IQR, -0.81 to 1.02); P = 0.001). Baseline T2* Z-score was also significantly lower in those pregnancies that subsequently delivered a SGA neonate (n = 23) compared with those that delivered a non-SGA neonate (n = 62) (median, -0.75 (IQR, -3.48 to 0.29) vs 0.35 (IQR, -0.79 to 1.05); P = 0.01). CONCLUSIONS: Our study confirms a BOLD effect in the human placenta and that baseline T2* values are significantly lower in pregnancies with FGR. Further studies are needed to evaluate whether such parameters may detect placental insufficiency before it has a clinical impact on fetal growth. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

A host species-informative internal control for molecular assessment of African swine fever virus infection rates in the African sylvatic cycle Ornithodoros vector.

African swine fever virus (ASFV) infection in adult Ornithodoros porcinus (Murry 1877, sensuWalton 1979) ticks collected from warthog burrows in southern and East Africa was assessed using a duplex genomic amplification approach that is informative with respect to the invertebrate host species and infecting sylvatic cycle virus. DNA extracted from individual ticks was used as template for the simultaneous amplification of a C-terminal 478-bp ASFV p72 gene region and a approximately 313-bp fragment of the tick mitochondrial 16S rRNA gene, under optimized reaction conditions. Within-warthog burrow infection rates ranged from 0% to 43% using this approach, and phylogenetic analysis of 16S gene sequences revealed the presence of three geographically discrete O. porcinus lineages, but no support for subspecies recognition. False negatives are precluded by the inclusion of host species-informative primers that ensure the DNA integrity of cytoplasmically located genome extracts. In addition, infection rate estimates are further improved as false positives arising from carry-over contamination when performing a two-step nested polymerase chain reaction are negated by the one-step approach. Phylogenetic comparison of full-length virus gene sequences with the partial C-terminal p72 gene target confirmed the epidemiological utility of the latter in a sylvatic setting. The method is therefore of particular value in studies assessing the prevalence and diversity of ASFV in relation to the African sylvatic tick vector and holds potential for investigating the role of alternative tick species in virus maintenance and transmission.

[Abnormalities of umbilical-portal circulation: From screening to diagnosis]. / Anomalies de la circulation ombilico-portale : du dépistage au diagnostic.

Abnormalities of umbilical-portal circulation are rare pathologies whose detection points in screening ultrasound are poorly taught. It can present as an unusual looking portal sinus, an abnormal trajectory of the umbilical vein, an anechoic intrahepatic image or more rarely as cardiomegaly. This can also be detected in the context of investigations of fetus with intrauterine growth retardation. Subsequently, the starting point of the diagnostic approach is based on the following dichotomy: does the umbilical vein penetrate or not into the liver, followed by systematic analysis of the trajectory and size of the umbilical-portosystemic vessels with color Doppler. Determining the prognosis of this abnormality, which varies according to the type, is a major challenge and by further studying this disorder in this project, it will help define what surveillance is required and subsequently help decide the most appropriate place for delivery.

Fusion Imaging to Guide Thoracic Endovascular Aortic Repair (TEVAR): A Randomized Comparison of Two Methods, 2D/3D Versus 3D/3D Image Fusion.

PURPOSE: To compare the accuracy of two-dimensional (2D) versus three-dimensional (3D) image fusion for thoracic endovascular aortic repair (TEVAR) image guidance. MATERIALS AND METHODS: Between December 2016 and March 2018, all eligible patients who underwent TEVAR were prospectively included in a single-center study. Image fusion methods (2D/3D or 3D/3D) were randomly assigned to guide each TEVAR and compared in terms of accuracy, dose area product (DAP), volume of contrast medium injected, fluoroscopy time and procedure time. RESULTS: Thirty-two patients were prospectively included; 18 underwent 2D/3D and 14 underwent 3D/3D TEVAR. The 3D/3D method allowed more accurate positioning of the aortic mask on top of the fluoroscopic images (proximal landing zone error vector: 1.7 ± 3.3 mm) than was achieved by the 2D/3D method (6.1 ± 6.1 mm; p = 0.03). The 3D/3D image fusion method was associated with significantly lower DAP than the 2D/3D method (50.5 ± 30.1 Gy cm2 for 3D/3D vs. 99.5 ± 79.1 Gy cm2 for 2D/3D; p = 0.03). The volume of contrast medium injected was significantly lower for the 3D/3D method than for the 2D/3D method (50.6 ± 22.9 ml vs. 98.4 ± 47.9 ml; p = 0.002). CONCLUSION: Higher image fusion accuracy and lower contrast volume and irradiation dose were observed for 3D/3D image fusion than for 2D/3D during TEVAR. LEVEL OF EVIDENCE: II, Randomized trial.

Involvement of the Zn-binding region of tetanus toxin in B and T recognition. Influence of Zn fixation.

Tetanus toxin contains a metal-binding site for zinc, located in its light chain. The sequence accounting for Zn fixation is part of a predicted amphipathic helical secondary structure and corresponds to a putative T cell epitope according to Rothbard and Taylor (EMBO J. 7, 93-100, 1988). In this paper, we analyse the antigenic properties of two synthetic peptides (233-248 = P12 and 225-243 = P13) containing the Zn binding sequence. Our results show that peptide P13 contains a B and T epitope. The B epitope seems to be immuno-dominant whether the T epitope is at least DR2 restricted. Zn binding on P13 leads to a decrease in its recognition by both antibodies and T lymphocytes.

Antigenic analysis of African measles virus field isolates: identification and localisation of one conserved and two variable epitope sites on the NP protein.

Measles virus isolates from epidemics in the Cameroons (1983) and Gabon (1984) were analysed by a panel of monoclonal antibodies against four of the virion proteins. We observed no antigenic variation in the haemagglutinin, the fusion glycoprotein, or in the matrix protein. However, both inter- and intra-epidemic variation was observed in the nucleoprotein (NP). On the basis of strain reactivity and a competition binding assay, three epitopic sites were designated on the NP. One site was found on all the measles virus strains examined, whereas the other two were variable. Examination of proteolytic cleavage of the NP in situ (on the ribonucleoparticle) showed that the conserved site is located on a large fragment which remains bound to the viral genome. The peptide removed by proteolysis contained the two variable epitopes. The variability of the NP is discussed in relationship to its biological activity.

Systematic genetic study of Alzheimer disease in Latin America: mutation frequencies of the amyloid beta precursor protein and presenilin genes in Colombia.

Nearly all mutations in the presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid beta precursor protein (APP) genes lead to early-onset Alzheimer disease (EOAD, onset age at or before 65 years). In order to assess the genetic contribution of these genes in a series of Colombian AD cases, we performed a systematic mutation analysis in 11 autosomal dominant, 23 familial, and 42 sporadic AD patients (34% with age of onset < or = 65 years). No APP missense mutations were identified. In three autosomal dominant cases (27.2%), two different PSEN1 missense mutations were identified. Both PSEN1 mutations are missense mutations that occurred in early-onset autosomal AD cases: an I143T mutation in one case (onset age 30 years) and an E280A mutation in two other cases (onset ages 35 and 42 years). In addition, a novel PSEN1 V94M mutation was present in one early-onset AD case without known family history (onset age 53 years) and absent in 53 controls. The E318G polymorphism was present in five AD cases and absent in controls. In PSEN2, two different silent mutations were detected, including one not reported elsewhere (P129). The majority of the Colombian AD cases, predominantly late-onset, were negative for PSEN and APP mutations.

[Integrins and metalloproteinases: an efficient collaboration in the invasive process]. / Intégrins et métalloprotéinases: une collaboration efficace dans le processus invasif.

During the invasive process, tumor cells must move through the extracellular matrix. They have to adhere to the extracellular matrix components, then proteolyse them and migrate on their fragments. This implicates integrins and proteinases, namely metalloproteinases. Numerous experiments which had been performed on various models, namely malignant melanomas proved that integrins have a major role in the transduction of signals from the outside to the inside of the cells, such signals enhancing the expression of the metalloproteinases or, in the contrary, inhibiting it. The modifications of this expression are dependent of extracellular matrix components and may be induced by the linking of specific antibodies to integrins. In some instances, the integrins localized on the tumor cell surface may act as receptors for extracellular matrix proteins and metalloproteinases at once, that may give to tumor cells an higher efficiency in the invasive process. Such mechanisms may result in interesting clinical perspectives for the control of metalloproteinases regulation in pathological processes.

[Effects of endocrine peptides on proliferation, migration and differentiation of human endothelial cells]. / Effets des peptides endocrines sur la prolifération, la migration et la différenciation des cellules endothéliales humaines.

AIMS: We aimed to evaluate the effects of several peptides (substance P, VIP, neuropeptide Y, bombesin, glucagon and somatostatin) on the proliferation, migration and differentiation of human endothelial cells and their modulation by an anti-angiogenic factor, endostatin. METHODS: Human endothelial cells (HUVEC) were isolated from umbilical veins. Their proliferation was measured by the incorporation of tritiated thymidine. Their migration was evaluated by using an haptotactic assay performed in Boyden chambers, after metabolic labeling of HUVEC through (35) S-methionin. Differentiation was evaluated as the capacity for HUVEC to form capillaries. RESULTS: Endothelial cell proliferation was increased by neuropeptide Y, bombesin and glucagon. Somatostatin induced a significant decrease in basal and stimulated endothelial cell proliferation. The migration of HUVEC increased in the presence of substance P, VIP, neuropeptide Y, bombesin, glucagon and somatostatin. The number of capillaries was increased by substance P and VIP and decreased by neuropeptide Y, bombesin and somatostatin. Endostatin induced a significant decrease in endothelial cell proliferation in the basal state and after stimulation by neuropeptide Y and bombesin. Endostatin had no additive effect on the anti-proliferative action of somatostatin. CONCLUSIONS: Our results suggest a role for endocrine peptides in the regulation of tumor angiogenesis. The potent anti-angiogenic effect of somatostatin may promote new therapeutic strategies.

[Juvenile arteriosclerotic leukoencephalopathy: anatomoclinical study of a case]. / Leucoencéphalopathie artériopathique juvénile: étude anatomoclinique d'un cas.

A 34-year old right-handed man was suffering from recurrent cerebro-vascular insults. CT-scans revealed several subcortical lacunar infarcts, and leukoaraïosis. Arteriography of the left and the right carotid arteries was performed respectively on the 4th and the 9th year of the disease, and did not elicit significant extracranial and intracranial vascular lesions. There were no arguments in favor of infectious, inflammatory, or auto-immune vascular diseases. The patient had tardive hypertension and dementia, and died at the age of 44. Pathological findings, limited to the brain and cervical spinal cord, revealed numerous ischemic lacunar infarcts. Histological lesions were consistent with the diagnosis of arteriosclerotic leukoencephalopathy. There were oedema, palor, and loss of myelin in the white matter, and nonspecific diffuse arteriosclerotic lesions that were particularly pronounced in the intimal part of the arterial wall. No inflammatory process nor amyloid deposits were found. Despite the onset of the disease in a young adult and the late occurrence of hypertension, our case report shares most of the pathological features of the Binswanger's type of arteriosclerotic encephalopathy.

APOE epsilon4 and Alzheimer's disease: positive association in a Colombian clinical series and review of the Latin-American studies.

OBJECTIVE: As the strength of the association between the APOE epsilon4 allele and Alzheimer's disease (AD) varies across ethnic groups, we studied if there was such an association in Colombian patients. METHOD: We performed apolipoprotein E (APOE) genotyping in a clinical sample of 83 unrelated AD patients, predominantly late-onset (>65 yrs) including familial ( n =30) and sporadic AD cases (n= 53) diagnosed according to NINCDS-ADRDA criteria and assessed by a multi-disciplinary team. Control subjects (n = 44) had no significant cognitive impairment by medical interview and neuro-psychological testing. RESULTS: We found a high association (OR= 5.1 95%CI 1.9 -13.6) between APOE epsilon4 and AD, in this series with predominantly late-onset cases with familial aggregation in 24 cases (28.9%). A significant negative association was found between epsilon2 and AD (OR= 0.2 95% CI 0.05-0.75). CONCLUSION: Further population-based surveys in Colombia are warranted to precise a possible dose effect of APOE epsilon4.

[Wilson's disease in an adult]. / Maladie de Wilson chez l'adulte.

PURPOSE: Wilson's disease (WD) is an inherited disorder of copper metabolism, characterized by the accumulation of copper in the body due to defective biliary copper excretion by hepatocytes. We report a series of 19 patients with WD. PATIENTS AND METHODS: This is a retrospective and descriptive case series of patients with WD followed in two hospitals of North East of France. RESULTS: Eight men and 11 women were studied. Median follow-up time was 16 years, median age at diagnosis was 18 years (range: 5-71 years). Median age at first symptom was 16 years. In addition to four cases diagnosed by familial screening, clinical manifestations at diagnosis were fatigue (n=5), jaundice (n=5), bleeding (n=1), abnormal movement disorders (n=2) and fortuitous (n=2). Cirrhosis was identified in 14 patients, neurological involvement occurred in seven patients and four patients presented with psychiatric disorders. d-penicillamine was the first treatment in 18 patients, discontinued for severe adverse events in seven patients. Trientine or zinc salts were then prescribed. Medical treatment was successful in 13 patients, but five patients underwent liver transplantation. Haemochromatosis was associated in one case, and one patient developed cholangiocarcinoma. CONCLUSION: WD is severe. Medical treatment allows disease control if it is correctly observed. Conversely, worsening with irreversible damage can occur if the treatment is discontinued.

Comparative tumor morphogenesis of two human colon adenocarcinoma cell clones xenografted in the immunosuppressed newborn rat.

Two clones derived from the human adenocarcinoma cell line LoVo, E2 and C5 xenografted subcutaneously to immunosuppressed newborn rats, respectively produced well-differentiated and undifferentiated tumors. The comparative morphogenesis of these tumors was performed on xenografts explanted as early as 18 h and up to 21 days after grafting by studying the progressive setting of the enterocyte differentiation marker dipeptidylpeptidase IV, the basal lamina component laminin and the alpha 6 integrin subunit. E2 xenografts which were entirely undifferentiated 18 h after grafting, presented well-polarized acini-like tumoral islets 6 h later, i.e. only 1 day after injection. Basement membranes, which were not organized at this moment, may not be necessary for morphological polarization. The chronology of function antigens polarization was characterized by formation of a basement membrane 5 days after the graft with associated basal sorting of alpha 6 integrin. The polarization of alpha 6 integrin took, however, longer to be achieved while apical addressing of dipeptidylpeptidase IV was the last to be completed. In contrast, C5 tumors never differentiated. Even 21 days after grafting alpha 6 integrin remained pericellular, dipeptidylpeptidase IV was underexpressed and laminin was found as perilobular patches. Quantitative differences in laminin or alpha 6 integrin expression could not account for the differences in the polarization process observed in the two variants.

Different fates of hepatitis B virus markers during plasma fractionation: a clue to the infectivity of blood derivatives.

Hepatitis B surface antigen (HBs Ag) and associated particles, e antigen (e Ag) and DNA polymerase are unevenly distributed during Cohn's cold ethanol fractionation of plasmas positive for these markers of the hepatitis B virus (HBV). Most of the e Ag, Dane particles and DNA polymerase are retained in fraction III whereas the bulk of HBs Ag is recovered in fraction IV where only 22 nm spheres and short filaments are still identified. These results suggest that differences in quantitative distribution of HB virions together with alteration of infectious particles during the fractionation process may in addition to heat inactivation account for the relative hepatitis risk of the various plasma derivatives.

Changes in the hypothalamo-corticotrope axis after bilateral adrenalectomy: evidence for a median eminence site of glucocorticoid action.

Bilateral adrenalectomy (ADX) leads to increased ACTH synthesis and secretion. It is thought that endogenous glucocorticoids exert a feedback mechanism at both pituitary and brain levels. The present study has been performed in order to determine the effect of ADX on the release of hypothalamic neuropeptides with corticotropin-releasing activity (CRA) and if there exists a median eminence site of glucocorticoid action to regulate hypothalamic-pituitary-adrenal (HPA) function. Adrenalectomized and sham-operated male rats were killed at different periods after surgery (2, 5, 7 and 14 days) and trunk blood was collected for ACTH and corticosterone (B) concentrations measurement. Brain (median eminence, ME; and medial basal hypothalamus, MBH) and pituitary (anterior lobe, AP; and neurointermediate lobe, NIL) tissues were dissected in order to evaluate either peptide content or in vitro hormone release. The results indicate that ADX blunted plasma B levels and increased AP ACTH content and secretion in a time-related fashion up to the 14th day. ADX significantly decreased both CRF and CRA contents in the ME at all periods studied; ME arginine-vasopressin (AVP) increased 7 and 14 days after ADX. MBH CRF decreased after ADX, but returned to sham value 2 weeks later; similarly, MBH AVP decreased at all periods after ADX. Removal of endogenous glucocorticoids did not vary neither oxytocin (OXY) content in the ME and MBH nor AVP and OXY contents in the NIL. In our superfusion experiments, we found that ADX increased basal AVP release and did not change spontaneous CRF secretion from ME terminals. Dexamethasone (Dxm, 10 nM) diminished AVP but not CRF output by ME tissues from adrenalectomized rats. A direct relationship was found between ME CRF and 28 mM KCl (hK+)-induced CRF release by MEs from adrenalectomized rats. ME fragments from adrenalectomized rats were hyperresponsive to kH+ stimulation of AVP release. Dxm (10 nM) decreased the hK(+)-evoked CRF and AVP release by MEs from adrenalectomized rats. ADX and dexamethasone treatment did not influence basal and hK(+)-elicited ME OXY release. Additionally, a rapid glucocorticoid inhibitory effect on ACTH secretion by isolated AP cells from both sham and adrenalectomized rats was found, and an in vitro corticotrope hyporesponse to 0.63 nM CRF and 9.25 nM AVP stimulation during several days after ADX.(ABSTRACT TRUNCATED AT 400 WORDS)

Disulfide linkage between C3b and tetanus toxin on tetanus toxin-specific EBV-transformed B cells.

EBV-transformed B cells specific for tetanus toxin were found to bind C3b in excess over the expected figures based on the number of complement receptors CR1. This was confirmed by analysis of cell extracts by SDS-PAGE giving evidence for C3b-membrane protein complexes that were disrupted upon reduction. Alkylation of C3b-free cysteine abolished formation of these complexes and only a noncovalent binding of C3b to CR1 was observed, which could be inhibited by mAb to CR1. When C3b was incubated with the same cells coated with tetanus toxin bound to their specific membrane Ig, preferential formation of disulfide-bonded complexes between tetanus toxin and C3b was observed. These observations correspond to a novel capacity of C3b to interact covalently through its cysteine 1010 with free SH groups of protein acceptors. One hypothesis is that the disulfide bond formation is catalyzed by a thioredoxin-like protein secreted and expressed on the membrane of EBV-transformed B cells. In the context of Ag processing and presentation by B cells, disulfide binding of chaperone C3b to Ag is likely to persist during transcytosis and to play a significant role in the modulation of the processing.