Observed-to-expected lung-area-to-head-circumference ratio on ultrasound examination vs total fetal lung volume on magnetic resonance imaging in prediction of survival in fetuses with left-sided diaphragmatic hernia.

OBJECTIVE: To assess and compare the value of antenatally determined observed-to-expected (O/E) lung-area-to-head-circumference ratio (LHR) on ultrasound examination vs O/E total fetal lung volume (TFLV) on magnetic resonance imaging (MRI) examination to predict postnatal survival of fetuses with isolated, expectantly managed left-sided congenital diaphragmatic hernia (CDH). METHODS: This was a multicenter retrospective study including all consecutive fetuses with isolated CDH that were managed expectantly in Mannheim, Germany, and in five other European centers, that underwent at least one ultrasound examination for measurement of O/E-LHR and one MRI scan for measurement of O/E-TFLV during pregnancy. All MRI data were centralized, and lung volumes were measured by two experienced operators blinded to the pre- and postnatal data. Multiple logistic regression analyses were performed to examine the effect on survival at hospital discharge of various perinatal variables, including the center of management. In left-sided CDH with intrathoracic herniation of the liver, receiver-operating-characteristics (ROC) curves were constructed separately for cases from Mannheim and the other five European centers and were used to compare O/E-TFLV and O/E-LHR in the prediction of postnatal survival. RESULTS: From Mannheim, 309 patients were included with a median gestational age (GA) at ultrasound examination of 29.6 (range, 19.7-39.1) weeks and median GA at MRI examination of 31.1 (range, 18.0-39.9) weeks. From the other five European centers, 116 patients were included with a median GA at ultrasound examination of 26.7 (range, 20.6-37.6) weeks and median GA at MRI examination of 27.7 (range, 21.3-37.9) weeks. Regression analysis demonstrated that the survival rates at discharge were lower in left-sided CDH (odds ratio (OR), 0.349 (95% CI, 0.133-0.918), P = 0.033) and those with intrathoracic liver (OR, 0.297 (95% CI, 0.141-0.628), P = 0.001), and higher with increasing O/E-TFLV (OR, 1.123 (95% CI, 1.079-1.170), P < 0.001), advanced GA at birth (OR, 1.294 (95% CI, 1.055-1.588), P = 0.013) and when birth occurred in Mannheim (OR, 7.560 (95% CI, 3.368-16.967), P < 0.001). Given the difference in survival rate between Mannheim and the five other European centers, ROC curve comparisons between the two imaging modalities were presented separately. For cases of left-sided CDH with intrathoracic herniation of the liver, pairwise comparison showed no significant difference between the area under the ROC curves for the prediction of postnatal survival between O/E-TFLV and O/E-LHR in Mannheim (mean difference = 0.025, P = 0.610, standard error = 0.050), whereas there was a significant difference in the other European centers studied (mean difference = 0.056, P = 0.033, standard error = 0.056). CONCLUSIONS: In fetuses with left-sided CDH and intrathoracic herniation of the liver, the predictive value for postnatal survival of O/E-TFLV on MRI examination and O/E-LHR on ultrasound examination was similar in one center (Mannheim), but O/E-TFLV had better predictive value compared to O/E-LHR in the five other European centers. Hence, in these five European centers, MRI should be included in the diagnostic process for left-sided CDH. © 2024 International Society of Ultrasound in Obstetrics and Gynecology.

Surface decoration of catanionic vesicles with superparamagnetic iron oxide nanoparticles: a model system for triggered release under moderate temperature conditions.

We report the design of new catanionic vesicles decorated with iron oxide nanoparticles, which could be used as a model system to illustrate controlled delivery of small solutes under mild hyperthermia. Efficient release of fluorescent dye rhodamine 6G was observed when samples were exposed to an oscillating magnetic field. Our system provides direct evidence for reversible permeability upon magnetic stimulation.

Simultaneously measuring the dichroism and the dielectric response of an azobenzene-doped organic glass former.

We have designed an experimental setup allowing to simultaneously measure both the dielectric response of a supercooled liquid and the dynamics of azobenzene chromophores dispersed in it. Both the azobenzene chromophores and the organic glass former have been synthesized with similar reaction paths: they are chemically similar, apart from the azobenzene group responsible for the strong optical absorption in the [350; 450 nm] range for the chromophores, while the embedding supercooled liquid is optically transparent. This material is deposited on transparent electrodes with an inter-electrode gap as small as 4 µm-obtained thanks to optical lithographic techniques. We show that our setup is sensitive enough to measure the coupling between the dielectric macroscopic response and the isomerization dynamics of 1% of chromophores excited by a 0.5-5 mW/cm2 light beam. We demonstrate that this coupling neither comes from the heating of the sample due to the light absorption nor from changes of the sample shape with light. Finally, we discuss the few physical effects, which may give rise to this coupling, and show that our experiment could test some recent predictions done in the framework of random first order transition theory of the glassy state.

Mortality and morbidity of preterm neonates weighing less than 750g: A 2-year retrospective cohort study.

BACKGROUND: The rate of premature births in France is 6% and is increasing, as is the rate of extremely premature births. Morbidity and mortality rates in this population remain high despite significant medical progress. We aimed to evaluate the morbidity and mortality rate in preterm neonates weighing<750g and to evaluate their outcome at 2 years' corrected age (CA). METHODS: This was a retrospective monocentric study including babies born between May 2011 and April 2013 who were preterm and weighed<750g. We evaluated mortality and morbidity in the neonatal period. At 2 years' CA, we focused on developmental quotient (DQ) with the Brunet-Lézine test, on neurosensory assessment (sleeping/behavior), and growth evaluation. RESULTS: Among the 107 infants included, 29 (27%) died in the neonatal period. Mean gestational age was 25.6 weeks' gestation. Female sex and higher birth weight were independent predictors of survival. A total of 61 (78.2%) infants showed extra-uterine growth retardation at 36 weeks' postmenstrual age. At 2 years' CA, 57 children were followed up; 38 were evaluated using the Brunet-Lézine test, 20 (52.6%) had a DQc<85, and none had a severe developmental delay (DQc<50). Six (10%) children had cerebral palsy and 22 of 56 (39.2%) showed language delay. Growth retardation persisted in 15 of 52 (28.8%) children. CONCLUSION: Our results confirm the acute fragility of extremely low-birth-weight babies with a high rate of morbidity and mortality. At 2 years' CA, this population still shows a considerable rate of mild difficulties, whose long-term evolution needs to be followed.

Experimental evidence of the electrostatic contribution to the bending rigidity of charged membranes.

We address the issue of the origin of the bending rigidity of a charged membrane formed from amphiphilic molecules. Electrostatic effects are investigated by direct measurement of the force necessary to deform a catanionic membrane as function of the ionic strength of the medium by means of an atomic force microscope (AFM). Using continuum mechanical modeling of membrane deformation, we derive the bending rigidity of the catanionic membranes and monitor for the first time its decrease in response to increasing salt concentration.

Enhancement of ricin A chain immunotoxin activity by perhexiline on established and fresh leukemic cells.

In the perspective of increasing the clinical potential of ricin A chain immunotoxins (RTA-ITs), perhexiline (Pex) and four structural analogues (Pex 2, Pex 3, Pex 7, and Pex 11) were evaluated for their ability to enhance RTA-IT activity in vitro. Only perhexiline significantly enhanced the cytotoxic activity of anti-CD5 RTA-ITs, T101 and T101-F(ab')2, on CEM III cell line (30- to 2000-fold), and of anti-HLA-DR RTA-IT, HNC-241, on both RAJI cell line (greater than 100-fold) and two immortalized cell lines originating from patients suffering from B-cell chronic lymphocytic leukemia, EHEB and FS2 D5 (10-fold). On 16 consecutive fresh B-cell chronic lymphocytic leukemia cell samples, significant T101-F(ab')2 RTA-IT and HNC-241 RTA-IT enhancement was observed with perhexiline which was comparable to that of NH4Cl and monensin. Perhexiline almost completely blocked RTA-IT intracellular degradation and profoundly modified its routing. These observations were linked to perhexiline-induced lipidosis via inhibition of sphingomyelinase activity. In conclusion, since the concentrations used are relevant with the pharmacokinetics of this agent, perhexiline appears to be a promising agent for in vivo enhancement of ricin A chain immunotoxins.

A mouse monoclonal antibody specific for the V beta 5.3 chain of the human TcR recognizes a subgroup of the mouse TcR V beta 8.2 chains.

We have analyzed the reactivity of a mouse monoclonal antibody directed against the human T cell receptor for antigen (TCR). This antibody (111-427) of immunoglobulin G1 isotype has been produced in a BALB/c mouse immunized with HPB-ALL cells and normal human peripheral blood leukocytes. It reacts specifically with the HPB-ALL lymphoma and 2 to 7% of normal human blood lymphocytes, on which it has a mitogenic effect in vitro. We have shown that it immunoprecipitates the alpha beta TCR of HPB-ALL and that it is specific for the V beta 5.3 chain of the human TCR. In addition, we have observed that this antibody stains a minor fraction of T lymphocytes in different strains of mice. We have screened a number of murine T cell clones or hybridomas and have found that the T cell hybrid line DO.11.10.S4.4 is positive. We have been unable to immunoprecipitate reproducibly the molecule recognized by 111-427 after 125I cell surface labeling and cell lysis in NP-40 or digitonin, probably because of low-affinity binding. On Western blotting, 111-427 revealed one band that has an apparent molecular mass of 89 kDa in nonreducing conditions and disappears after reduction. Similar results were obtained in parallel with the F23.1 and F23.2 antibodies. Thus, this antibody appears to recognize an epitope present primarily on the V beta 8.2 chain of the mouse TCR. We have assayed its capacity to stimulate splenic T lymphocytes in vitro. We have observed that it is capable of triggering, to a minor degree in soluble form and very effectively when coupled to Sepharose beads, the proliferation of spleen T lymphocytes from mice chronically infected with the blood parasite Trypanosoma cruzi.

Influence of a diet of fluoride-fed cockerels on reproductive performance of captive American kestrels.

In 1982, twenty-four pairs of captive American kestrels (Falco sparverius) were forced to renest by removal of their first clutches 6 days after their completion. Immediately following, each of three groups of eight pairs was randomly assigned to one of three daily dietary regimes for 10 days: (1) three 1-day old cockerels with background levels of F(-) (62.4+/-51ppm, mean+/-SD) in their femurae, (2) two 10-day old cockerels with 4512+/-810ppm of F(-) in their femurae, (3) two 10-day old cockerels with 7690+/-417ppm of F(-) in their femurae. Fluoride levels in femurae of treated kestrels were significantly (P<0.0025) higher than those of control birds. Clutch sizes tended to be smaller as more fluoride was added to the diet, but not significantly so, due to an increase of the variance in the treatment group. Per cent fertility and per cent hatchability were not significantly affected by treatment. The fluoride content in eggshells in the fluoride-treated groups differed significantly from those of the control group (P<0.001).

[Immunotoxins]. / Les immunotoxines.

Immunotoxins are conjugates between antibodies especially directed against cancer cells and a subunit of a powerful toxin. We used the A-chain of ricin. These conjugates are specifically cytotoxic when used at very low concentrations in vitro and can destroy more than 99.99% of clonogenic cells. The efficacy of immunotoxins was also demonstrated in vivo but is inferior to its in vitro potency. For this reason the first use of immunotoxins in man can be the cleaning up of bone marrow from leukemic cells in the near future.

The effect of dietary sodium fluoride on internal organs, breast muscle, and bones in captive American kestrels (Falco sparverius).

In 1982, 29 7-day-old American kestrel (Falco sparverius) chicks from captive stock were randomly assigned to one of three dietary regimens: (1) 10 birds were fed daily with cockerel mash (0 ppm of F-: control birds); (2) 10 birds were fed daily with cockerel mash containing 1,120 ppm of F-; (3) 9 birds were fed daily with cockerel mash containing 2,240 ppm of F-. Growth of the kestrels was not significantly affected by NaF in their diet. No significant differences were found among the 3 groups for length of duodenum, jejunum and ileum. Rectum was longer as more fluoride was added to the diet. Weights of adrenals, brain, gizzard, spleen, heart, kidneys, liver, pancreas, and pectoral muscle were not significantly affected by treatment, although kidneys, spleen and adrenals tended to become lighter. Percent bone ash was significantly (P less than 0.05) increased, while bone breaking strength was significantly (P less than 0.05) decreased by treatment.

Functional epitope analysis of the human CD4 molecule: antibodies that inhibit human immunodeficiency virus type 1 gene expression bind to the immunoglobulin CDR3-like region of CD4.

We recently demonstrated that monoclonal antibody (MAb) 13B8-2, specific for the immunoglobulin (Ig) complementary determining region 3 (CDR3)-like region of the CD4 molecule, inhibits viral transcription in human immunodeficiency virus (HIV)-infected CEM cells and HIV type 1 (HIV-1) promoter activity. Here, we have studied the capacity of several MAb specific for the D1 domain of CD4, including anti-CDR2-like (Leu-3a and ST4) and anti-CDR3-like (13B8-2 and ST40) MAb, and for the D2 domain of CD4 (BL4) to inhibit both provirus transcription in HIV-1LAI-infected CEM cells and transcription of the chloramphenicol acetyltransferase (CAT) gene under control of the HIV-1 long terminal repeat in transiently transfected CEM cells. We found that HIV-1 promoter activity and provirus transcription are inhibited only by MAb that bind to the CDR3-like region in domain 1 of CD4. Moreover, we demonstrated that the Fab fragment of an anti-CDR3-like region-specific anti-CD4 MAb is a powerful inhibitor of HIV-1 promoter activity. These results have implications for understanding the role of the CDR3-like region in CD4 T-cell signaling, which controls provirus transcription.

Endocytosis of an antibody ricin A-chain conjugate (immuno-A-toxin) adsorbed on colloidal gold. Effects of ammonium chloride and monensin.

An immunotoxin (IT) formed by a specific antibody coupled to the ricin A chain was adsorbed on colloidal gold particles (IT-Au). Binding and internalization of IT-Au in human lymphoblastic CEM cells were studied using electron microscopy. IT-Au showed specific cytotoxic activity toward the target cells. After 1 h at 4 degrees C, IT-Au were linked diffusely to the plasma membrane with 45% of the particles regrouped in clusters. Upon transfer to 37 degrees C, the particles carrying the ligand were regrouped more frequently and internalized into the cell by endocytosis through smooth microinvaginations or coated pits of the plasma membrane. After 15 min, IT-Au was observed in endocytic vacuoles, or receptosomes, in tubular structure near the Golgi apparatus and in lysosomes. Entry of IT-Au into lysosomes was rapid (around 50% of intracellular IT-Au particles after 30 min). NH4Cl or monensin, well-known potentiators of immunotoxin activity, when present in incubation medium, altered neither the processes nor the rate of IT-Au endocytosis. In the presence of either of these substances, IT-Au accumulated in the normal or often enlarged endocytic vacuoles, and entry into the lysosomes was slowed down (50% of particles after 2 h 15 min). We conclude that this intense slowing-down in the speed of IT-Au transportation into lysosomes and the functional modifications of these organelles help to explain the increased efficacy of immunotoxins in the presence of potentiators.

[Stereological analysis of normal Papio Papio liver parenchymal cells (author's transl)]. / Analyse stéréologique du parenchyme hépatique chez le singe babouin (Papio papio).

Stereological analysis of normal Papio Papio liver parenchymal cells has been performed according to the method of Weibel (1969). The study was carried out on liver samples collected from 3 males and 3 females. Sampling was done at three levels of magnification (X 250, X 5 000, X 15 000) without taking into consideration the lobular variations. The lobular stereological model included the hepatocyte, all the cellular organelles and the extra-hepatocytic space compartment. Surface and volume densities were determined; the results are given with respect to three reference units : 1 cm3 lobular tissue, 1 cm3 hepatocyte and 1 cm3 hepatocytic cytoplasm. The mean volume of the Baboon hepatocyte and its components were also measured. Statistical analysis of the results did not show wide individual variation in the population studied. The volume densities of the components were compared to those of rat, dog and man as determined by other investigators. The hepatocytes constitute 84,9% of the lobular volume, and the extra-hepatocytic space 15,1%. The mean individual volume of the hepatocyte is 6 470 micrometer3, which is higher than in rat and dog. The smooth endoplasmic reticulum has a much higher surface density (3,93 m2/cm3) than that of the rough endoplasmic reticulum (1,53 m2/cm3). The values obtained in the present study can be used as reference values in the evaluation of experimentally induced hepatic modifications in Baboon.

[The mammary gland of the male rat: a histological, histochemical and ultramicroscopic study (author's transl)]. / Etude de la glande mammaire du rat male. Aspects histologiques, histochimiques et ultrastructuraux.

Results of a histological, histochemical and ultramicroscopic study of samples taken from the mammary glands of male Wistar, Sprague-Dawley and Long Evans untreated rats, aged about 8 weeks, are reported. Lobulo-alveolar epithelial formations were observed together with increased metabolic and secretory activity, more frequent in Wistar rats than in other strains. No visible morphological abnormality was noted in the genital tract or adenohypophysis. There was no sign of feminization. The same findings were observed in male Wistar and Sprague-Dawley rats given three different diets of which one was semi-synthetic. The possibility of an exogenous mammotropic dietary factor is therefore very improbable. Endogenous hormonal stimulation, especially consecutive increases in oestrogens and prolactin in the prepubertal period, is possibly the cause of development of mammary tissue. These results show that the mammary gland, in the normal male rat, is not inactive. It seems, therefore, that this organ is not a suitable model for the evaluation of experimental mammotropic effects.

Antigenic modulation induced by four monoclonal antibodies adsorbed on gold particles (specificity anti-CD4, anti-CD5, anti-CD7, and anti-150-kDa antigen): relationship between modulation and cytotoxic activity of immunotoxins.

The present study concerns the antibody-induced antigenic modulation of CD4, CD5, CD7, and 150-kDa antigens present on cells of the CCRF-CEM human T line. The immunogold electron microscopy method was used, and it was found that the entry routes associated with the various antigen-antibody complexes were different. Thus, the anti-CD7 monoclonal antibody (MoAb) was frequently internalized via the coated structures of the cell membrane, whereas anti-CD5 MoAb was rarely internalized via those structures and anti-CD4 and anti-150-kDa antigens never used this route. The delay required for 50% internalization of the labeled MoAb-receptor complexes was 30 min. 1 h, 2 h, and 9 h for anti-CD7, anti-CD5, anti-CD4, and anti-150-kDa antigen MoAbs, respectively. A shedding of complexes from the cell surface was never observed. The internalized labeled MoAbs were sequentially transferred into endocytic vacuoles, then into fine anastomosed tubulovesicular structures, and then into lysosomes. However, the anti-150-kDa antigen MoAb proceeded directly from endocytic vacuoles to lysosomes. Among the four MoAbs studied, anti-CD7 MoAb was the most abundant in the endosomal compartment (up to 34% of internalized particles) before it proceeded to the lysosomes. The overall valency of the anti-CD7 MoAb-labeled beads (from 3.8 to 14 MoAb molecules per bead) did not modify the intracellular routing. These results suggested that the subcellular fate of MoAbs was an intrinsic property of each MoAb-antigen complex. More importantly, the comparison between the MoAb-induced modulation and the cytotoxic level of the immunotoxin built with the same MoAb suggested that receptor-mediated endocytosis via coated pits, along with an abundant occurrence of the antigen-MoAb complex within the endosomal complex, could correspond to the best set of conditions for the transfer of the toxin moiety of the immunotoxin to the cytosol.

Effects of morphine, naloxone, d,l-cyclazocine, and d-amphetamine on behaviour controlled by a schedule of interresponse time reinforcement.

The separate effects of graded doses of morphine, naloxone, d,l-cyclazocine, and d-amphetamine on responding maintained by a differential reinforcement of low rate schedule of food presentation were examined in rats. Morphine did not alter response rates at doses of 1--5.6 mg/kg; at 10 mg/kg a 57% decrease in responding was observed and behaviour was even more severely depressed by 30 mg of morphine per kilogram. Naloxone did not affect responding at doses ranging from 0.1 to 10 mg/kg. d,l-Cyclazocine at doses of 3 and 5.6 mg/kg induced substantial increases in responding not observed when the dose was increased to 10 mg/kg. Cyclazocine, as well as morphine, produced dose-dependent decreases in the number of reinforcements per session. d-Amphetamine exerted a biphasic effect on responding; small doses increased response rates (0.3--3 mg/kg) and responding was suppressed by the drug at a dose of 10 mg/kg. Behaviourally active doses of d-amphetamine caused a dose-dependent reduction in the number of reinforcements per session. Naloxone at otherwise inactive doses (1--10 mg/kg) was found, in separate experiments, to antagonize the rate-decreasing effects of morphine, and to reduce the rate-increasing effects of d-amphetamine. The latter effect is not easily interpreted but confirms and extends other research employing rats in which naloxone was found to reduce the rate-increasing effects of small doses of d-amphetamine upon locomotor activity and responding maintained by a continuous electric-shock postponement procedure. In additional experiments morphine was given daily for 25 consecutive sessions at a dose of 30 mg/kg, 5 min preceding each test session. Responding was suppressed throughout this period and the dose of morphine given before each session was reduced to 10 mg/kg for 35 further sessions. Tolerance to the rate-decreasing effects of morphine was demonstrated; naloxone given in conjunction with morphine (10 mg/kg) in morphine-tolerant rats restored to control values the number of reinforcements per session without causing significant change in overall rates of responding. Few experiments have dealt previously with the development of tolerance to the behavioural effects of morphine under comparable dose regimens, time-course relationships, or behavioural testing procedures. Systematic analyses of these interrelated variables are needed since it is now evident that the schedule employed to maintain responding itself exerts significant effects.

Golgi vacuolization and immunotoxin enhancement by monensin and perhexiline depend on a serum protein. Implications for intracellular trafficking.

Vacuole formation around the Golgi and immunotoxin enhancement induced by low doses of the ionophore monensin were inhibited by 50% human plasma (final concentration), whereas the lysosomal pH increase remained unaffected. Immunotoxin enhancement by the Ca2+ antagonist perhexiline was also inhibited by plasma. The inhibiting factor was present in different species and highly concentration-dependent. After purification on DEAE- and CM-Sepharose it showed a heterogeneous distribution between 45 and 50 kDa, in sodium dodecyl sulfate-polyacrylamide gel electrophoresis, an extreme isoelectric point near 3.5, and binding to wheat germ agglutinin-Sepharose. Maximum inhibition was found in the lower molecular mass fraction of 45 kDa. The 50-kDa fraction, although showing immunological identity reactions, remained almost inactive. The simultaneous inhibition of morphological alterations and the enhancement of immunotoxin activity by the highly enriched protein provides a first direct link between both events. Apart from a role of this serum glycoprotein on in vivo inhibition of immunotoxin enhancement, its ability to maintain normal intracellular trafficking in the presence of blocking agents, such as monensin and perhexiline, suggests a more fundamental role in the regulation of these mechanisms.

Triiodothyronine-secreting (toxic) adenoma of the thyroid gland: light and electron microscopic characteristics.

A patient with thyrotoxicosis due to a triiodothyronine (T3)-secreting autonomous adenoma is described. The histmorphology of the neoplasms was similar to other neoplasms previously reported. Ultrastructural features of the adenoma are compatible with a very actively secreting follicular cell and are best compared with the ultrastructure of a diffuse toxic goiter. Distinctive features that separate toxic adenomas from various thyroid carcinomas and normal thyroid parenchyma are discussed.