Measurement of the cosmic microwave background polarization lensing power spectrum with the POLARBEAR experiment.

Gravitational lensing due to the large-scale distribution of matter in the cosmos distorts the primordial cosmic microwave background (CMB) and thereby induces new, small-scale B-mode polarization. This signal carries detailed information about the distribution of all the gravitating matter between the observer and CMB last scattering surface. We report the first direct evidence for polarization lensing based on purely CMB information, from using the four-point correlations of even- and odd-parity E- and B-mode polarization mapped over ∼30 square degrees of the sky measured by the POLARBEAR experiment. These data were analyzed using a blind analysis framework and checked for spurious systematic contamination using null tests and simulations. Evidence for the signal of polarization lensing and lensing B modes is found at 4.2σ (stat+sys) significance. The amplitude of matter fluctuations is measured with a precision of 27%, and is found to be consistent with the Lambda cold dark matter cosmological model. This measurement demonstrates a new technique, capable of mapping all gravitating matter in the Universe, sensitive to the sum of neutrino masses, and essential for cleaning the lensing B-mode signal in searches for primordial gravitational waves.

Evidence for gravitational lensing of the cosmic microwave background polarization from cross-correlation with the cosmic infrared background.

We reconstruct the gravitational lensing convergence signal from cosmic microwave background (CMB) polarization data taken by the Polarbear experiment and cross-correlate it with cosmic infrared background maps from the Herschel satellite. From the cross spectra, we obtain evidence for gravitational lensing of the CMB polarization at a statistical significance of 4.0σ and indication of the presence of a lensing B-mode signal at a significance of 2.3σ. We demonstrate that our results are not biased by instrumental and astrophysical systematic errors by performing null tests, checks with simulated and real data, and analytical calculations. This measurement of polarization lensing, made via the robust cross-correlation channel, not only reinforces POLARBEAR auto-correlation measurements, but also represents one of the early steps towards establishing CMB polarization lensing as a powerful new probe of cosmology and astrophysics.

Anticancer activities of pomegranate extracts and genistein in human breast cancer cells.

Previous studies have demonstrated the anticarcinogenic activity of pomegranate extracts and genistein in a series of human cancer cells. In the present study, the potential anticancer effects of pomegranate extracts and genistein on inhibition of cell proliferation and induction of apoptosis in human breast cancer cells was investigated. Human breast cancer cells (MCF-7) were cultured as monolayers in complete RPMI 1640 medium. The cells were cultured for 48 hours to allow growth and achieve about 80% confluence in 48-well culture plates, and then exposed to the agents for 24 hours in single and combination treatments. Post-treatment growth rate and apoptosis induction were assessed by the use of a series of bioassays-lactate dehydrogenase and 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium (inner salt) for viability and cytotoxicity; acridine orange-ethidium bromide and terminal deoxyribonucleotidyl transferase-mediated dUTP nick-end labeling assays for induction of apoptosis. Both pomegranate extracts and genistein had significant (dose- and time-dependent) cytotoxic and growth inhibition effects on MCF-7 cancer cells. Both growth inhibition and cytotoxicity were significantly higher (P < .01) in the combination treatments than in the single treatments with either agent. The data revealed that both drugs in single and in combination treatments induced apoptosis in MCF-7 cells. Apoptotic induction in the combination treatments was significantly higher (P < .01) than in single treatments. Both pomegranate extracts and genistein inhibit the growth of MCF-7 breast cancer cells through induction of apoptosis, with combination treatment being more efficacious than single treatments.

The in vitro and ex vivo antioxidant properties, and hypolipidemic activity of CGP 2881.

This report describes the in vitro and ex vivo antioxidant properties of a new antioxidant, CGP 2881. This compound is structurally similar to probucol, in that both compounds contain bis-tertiary butyl phenyl groups. However, CGP 2881 consistently inhibited CuSO4 (Cu2+)- and macrophage (MO)-induced oxidation of human low density lipoproteins (LDL) more potently than equimolar concentrations of probucol. CGP 2881 (1 mumol/l) prolonged the lag phase of diene formation during Cu(2+)-induced LDL oxidation by 3.4 versus 1.5-fold prolongation with 1 mumol/l probucol (P < 0.05 vs CGP 2881). The IC50 for inhibiting the formation of Cu(2+)-induced thiobarbituric acid-reactive substances (TBARS) was 0.15 mumol/l for CGP 2881, versus approximately 10 mumol/l for probucol. The IC50 for MO-induced oxidation of LDL (TBARS) was 0.64 mumol/l. In contrast, 1 mumol/l probucol failed to inhibit MO-induced oxidation of LDL. Treatment of cholic acid/cholesterol-fed rats with CGP 2881 (50 mg/kg per day, orally for 5 days) inhibited ex vivo Cu(2+)-induced oxidation (TBARS) of the very low density lipoproteins (VLDL) + LDL lipoprotein fraction by 93% versus vehicle controls (P < 0.0001), and prolonged the lag phase for Cu(2+)-induced diene formation by 3.4-fold over vehicle-treated controls. Five days of orally administered CGP 2881 reduced plasma total cholesterol and LDL cholesterol levels to 55 and 54% of vehicle-treated controls, respectively (P < 0.05). In contrast, probucol had no appreciable effect on plasma total cholesterol or LDL cholesterol levels, unless administered for longer than 5 days. Treatment of hypercholesterolemic rabbits with 50 mg/kg per day orally for 5-12 days delayed the lag phase of diene formation during LDL oxidation by 4.3-fold over controls. However, the relative antioxidant potencies of CGP 2881 and probucol seen with oral administration to hypercholesterolemic rabbits were reversed when the compounds were given intravenously. In addition, the effects of these antioxidants were potentiated when given to normocholesterolemic rabbits compared to hypercholesterolemic animals. These data establish that CGP 2881 demonstrates hypolipidemic activity and is a substantially more potent antioxidant than probucol (in vitro and ex vivo). CGP 2881 may be useful as a new antioxidant tool in the effort to better understand the atherogenicity of oxidized LDL (oxLDL).

CGP 43371 paradoxically inhibits development of rabbit atherosclerotic lesions while inducing extra-arterial foam cell formation.

Ansamycins are hypolipidemic compounds which, when administered to various animal species, dramatically lower high density lipoprotein (HDL) cholesterol levels, in addition to reducing the levels of other lipoprotein classes. The current study tested one of these ansamycins (CGP 43371) for its hypolipidemic and anti-atherosclerotic activity in cholesterol-fed rabbits. Rabbits were fed a 0.25% cholesterol-enriched diet with or without admixed CGP 43371, equivalent to 30 mg/kg per day for 16 weeks. Compared with control rabbits, CGP 43371 treatment lowered total cholesterol levels (46%, P<0.05) and lipoprotein cholesterol levels (HDL, 58%; VLDL, 49% [both P<0.05]; LDL, 28% [not significant]). Despite the dramatic lowering of HDL cholesterol levels, aortic atherosclerosis, assessed by grossly visible sudanophilia, was significantly inhibited versus controls (total aorta=38%; aortic arch=32%; thoracic aorta=60%). Of particular note in CGP 43371-treated rabbits was a striking splenomegaly, which correlated with the presence of massive accumulations of macrophage foam cells in the splenic red pulp. We speculate that CGP 43371 inhibits the development of atheroselerotic lesions in rabbits by both a hypolipidemic mechanism, and by a mechanism(s) in which macrophage foam cells accumulate in the spleen.

Diaminoindanes as microsomal triglyceride transfer protein inhibitors.

The synthesis and biological activities of biarylamide-substituted diaminoindanes as microsomal triglyceride transfer protein (MTP) inhibitors are described. One of the more potent compounds, 8aR, inhibited both the secretion of apoB from Hep G2 cells and the MTP-mediated transfer of triglycerides between synthetic acceptor and donor liposomes with IC(50) values of 0.7 and 70 nM, respectively. In normolipidemic rats and dogs, oral administration of 8aR dose-dependently reduced both plasma triglycerides and total cholesterol. Moreover, in rats and dogs, 8aR also prevented the postprandial rise in plasma triglycerides following a bolus administration of a fat load. Because MTP inhibitors decrease very low density lipoprotein assembly in the liver, the potential for hepatic lipid accumulation was evaluated. In normolipidemic rats, hepatic cholesterol and triglyceride contents were dose-dependently increased by 8aR. However, hepatic lipid accumulation resulted in negligible change in total liver weight and was reversible after withdrawal of the compound.

Effect of matrix metalloproteinase inhibition on progression of atherosclerosis and aneurysm in LDL receptor-deficient mice overexpressing MMP-3, MMP-12, and MMP-13 and on restenosis in rats after balloon injury.

The broad-spectrum MMP inhibitor CGS 27023A was tested to determine its potential as a therapy for atherosclerosis, aneurysm, and restenosis. LDL receptor-deficient (LDLr -/-) mice fed a high-fat, cholic acid-enriched diet for 16 weeks developed advanced aortic atherosclerosis with destruction of elastic lamina and ectasia in the media underlying complex plaques. Lesion formation correlated with a 4.6- to 21.7-fold increase in MMP-3, -12, and -13 expression. Treatment with CGS 27023A (p.o., b.i.d. at 50 mg/kg) had no effect on the extent of aortic atherosclerosis (36 +/- 4% versus 30 +/- 2% in controls), but both aortic medial elastin destruction and ectasia grade were significantly reduced (38% and 36%, respectively, p < 0.05). In the rat ballooned-carotid-artery model, CGS 27023A (12.5 mg/kg/day via osmotic minipump) reduced smooth muscle cell migration at 4 days by 83% (p < 0.001). Intimal lesions were reduced by 85% at 7 days (p < 0.001), but intimal smooth muscle proliferation was unaffected, and inhibitory efficacy was lost with time. At 12 days, intimal lesion reduction was less potent (52%, p < 0.01). At 3 and 6 weeks, reductions of 11% and 4%, respectively, were not significant. This demonstrates that it is essential to include late time points when the ballooned-carotid-artery model is employed to ensure that lesion size does not "catch up" when a compound solely inhibits smooth muscle cell migration. In summary, MMP inhibitor therapy delayed but did not prevent intimal lesions, thereby demonstrating little promise to prevent restenosis. In contrast, MMP inhibitor therapy may prove useful to retard progression of aneurysm.

[Neonatal screening of congenital hypothyroidism with TSH measurement in dried blood spots on filter paper. A two years experience (author's transl)]. / Dépistage néonatal de l'hypothyroïdie congenitale par le dosage de la TSH sur tache de sang séché. Expérience de 2 ans dans la région Rhône-Alpes.

Systematic screening for congenital hypothyroidism was started in Lyon in september 1976. This screening was coupled with PKU, using the same dried blood samples on filter paper obtained on the 5th day of life. TSH levels were determined by radioimmunoassay adapted for dried blood samples (Kit Abbott). In 24 months, 56 176 samples were analyzed. The critical level calling for control was successively raised from from 20 to 30, now 40 microUI/ml of serum. A high level of TSH was found in 307 children (0,55%). Pathological deliveries were found in most of these infants (neonatal injury, cesarean, section forceps or ocytocic perfusion, neonatal icterus) and a second or a third measurement showed normal TSH level. Congenital hypothyroidism, was found detected in 18 infants: 12 ectopic gland, 5 athyreosis and 1 dyshormonogenesis. Treatment was begun at a mean age of 38 days (29 to 50 days).

[Neonatal screening for congenital hypothyroidism by measuring TSH in dried blood samples. Two years experience in the method (author's transl)]. / Dépistage néonatal de l'hypothyroïdie congénitale par le dosage de la TSH sur tache de sang séché.

Systematic screening for congenital hypothyroidism was started in Lyon in September 1976. This screening was coupled with PKU screening, using the same dried blood samples in filter paper obtained on the 5 th day of life. TSH levels were determined by radioimmunoassay adapted for dried blood samples (Kit Abbott). In 24 months, 56 176 samples were analyzed. The critical level calling for control was successively raised from 20 to 30 now 40 muUl/ml of serum. A high level of TSH was found in 307 children (0.55 p. 100). Pathological deliveries were found in most of these infants (neonatal injury, cesarean section, forceps or ocytocic perfusion, neonatal icterus) and a second or a third measurement showed normal TSH level. Congenital hypothyroidism, was detected in 18 infants: 12 ectopic gland, 5 athyreosis and 1 dyshormonogenesis. Treatment was begun at a mean age of 38 days (29 to 50 days). Despite a short follow-up the psychomotor development of the infants seems to be normal in all cases but one (one athyreosis with a neonatal injury and a malformative syndrome).

[Analysis of mandibular movements in present-day humans by examination of the striae found on the facets of wear]. / Analyse des mouvements mandibulaires chez l'homme contemporain par l'observation des stries rencontrées sur les facettes d'usure.

The analysis of the microscopic appearance of the dental wear facets in contemporary european subjects has been conducted using the replica method. It showed the presence of numerous striae running in various directions. The angle of each stria with the sagittal plane was measured: 1540 angle values were recorded on 6 facet types belonging to 3 groups of teeth. Statistical analysis showed that the striae distribution on the various facets studied was not random. The facets of the palatal edges and facets of the upper central incisors showed mainly parasagittal striae indicating propelling movements. The striae of the wear facets of the canine tips showed no definite direction. The palatal facets of canines as well as the working and non-working facets of the molars showed 2 groups of striae oriented obliquely, forward and inside and also forward and outside. The molar working facets also had parasagittal striae. The significance of the 2 groups of oblique striae is discussed in relation to the occlusal kinematic during mastication.

Combined immunodeficiency disease associated with absence of cell-surface HLA-A and -B antigens.

An infant with a family history suggestive of immunodeficiency presented with combined immunodeficiency. No HLA-A and -B antigens were present on lymphocyte and platelet surfaces, but they were found in the serum. HLA-D determinants were present on lymphocytes. In spite of a fetal thymus transplantation, the infant died of infections associated with the immunodeficiency. The thymus and lymphoid organs were present but hypoplastic and contained few lymphocytes at postmortem examination. The finding of an immodeficiency associated with an absence of cell-surface HLA-A and -B antigens may be regarded as the consequence of the lack of cellular histocompatibility antigens on immune development. Alternatively, other membrane components may have also been defective and partly responsible for the observed abnormalities.

HIV risk perception, risk behavior, and seroprevalence among female commercial sex workers in Georgetown, Guyana.

A study of 108 female sex workers engaged in prostitution in Georgetown, Guyana, was made in April 1993. Based on interviews and procurement of blood samples, the study investigated relationships between HIV seroprevalences and AIDS knowledge, risk behaviors, client characteristics, and condom use. Street-walkers-as distinct from sex workers in bars, hotels, and Port Georgetown-tended to charge less, be worse off socioeconomically, and have clients who were similarly disadvantaged; they were therefore classified as belonging to a "lower" socio-economic stratum, while the other workers were classified as belonging to a "higher" stratum. The overall HIV seroprevalence found among the sex workers was 25% (95% CI: 17%-33%). But the 50 subjects in the lower stratum had a relatively high seroprevalence (42%, as compared to 10% among those in the higher stratum), accounting for 21 of the 27 HIV-seropositive subjects. Reported patterns of client origins (Guyanese or foreign), worker willingness to have sex without a condom, and condom use by clients differed by stratum. Participants in the higher stratum were more disposed to having sex without a condom. The workers' knowledge of what causes AIDS and how HIV is transmitted was low in both strata; substantial numbers of workers said they had contracted a sexually transmitted disease within the past two years or were users of illicit drugs. Condom use is reportedly less common among Guyanese than foreign clients, suggesting a greater risk of contracting HIV from Guyanese clients or infecting Guyanese clients with it. The HIV seroprevalence among workers who said they had only Guyanese clients was statistically greater than the rate among those who said they had only foreign clients. The HIV seroprevalence among those reporting more than five clients per week was statistically greater than among those reporting fewer. HIV seropositivity was relatively high among the 12 workers who said they used cocaine. Overall, the findings supported the view that interventions targeted at female sex workers and their clients should be strengthened-more specifically, that concerted efforts should be made to intensity condom promotion, distribution, and social marketing; to improve STD services that provide treatment and counseling for female sex workers; and to increase educational activities among the workers' Guyanese clients.

Kinetics of the HCG-induced steroidogenic response of the human testis. III. Studies in children of the plasma levels of testosterone and HCG: rationale for testicular stimulation test.

Little information is available regarding the time, rhythm, number, and appropriate dosage of human chorionic gonadotropin (HCG) for adequate testing of testicular function in human. The time course of the effect of two, three, or seven HCG injections at intervals of one, five, and two days, respectively, on the plasma levels of testosterone was studied in 11 boys. The first injection induced a progressive and modest rise of T. The second given one day later had little additive effect, maximal values being seen 72 to 120 hr later. In the prepubertal boys to whom several HCG injections were given, testosterone levels reached comparable levels after four injections every five days or seven injections every other day. Although the number of subjects studied was relatively small, these results give some rational basis for the following HCG test: two or four injections at four-day intervals.

[XY pure gonadal dysgenesis. Two cases report (author's transl)]. / Dysgénésie gonadique pure XY. A propos de deux observations.

Two cases of XY dysgenesis are reported. In one case, that of a 13 year-old girl presenting with impuberism, a gonadoblastoma was detected by histologic examination of the streak. In the second case, that of a 6 month-old girl, short stature and dysplasia of the nails suggested the diagnosis.

[Clinical significance of plasma renin, testosterone, 17-alpha-hydroxyprogesterone and ACTH activities in the treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. A review of 31 cases]. / Interet clinique des dosages plasmatiques d'activite renine, testosterone, 17-alpha-hydroxyprogesterone et A.C.T.H. au cours de la surveillance des hyperplasies congenitales des surrenales par deficit en 21-hydroxylase. A propos de 31 observations.

Measurements of urinary steroids do not allow a precise supervision of the evolution and treatment of congenital adrenal hyperplasia due to 21-hydroxylase deficiency. Thirty-one cases with a 2 year follow-up allowed a trial of estimation of the progress that could be obtained with plasmatic dosages of renine, testosterone, A.C.T.H. and 17-hydroxyprogesterone (17-O.H.P.) activities. The best way for reaching diagnosis is presently 17-O.H.P. However, the amplitude and variability of nyctemeral changes of 17-O.H.P. as well as A.C.T.H. activities do not allow to use these two dosages for a precise supervision of therapeutic effects. On the contrary, the dosage of testosterone allows the appreciation of the risk of virilization and its reliability gives a precise control of the effects of steroid therapy. The dosage of the renine activity disclosed unknown or not well controlled sodium-losses, and allowed to adjust the dosage of 9-alpha-fluorohydro-cortisone, while limiting glucocorticosteroids. It gave also evidence of the usefulness of prolonged steroid therapy until the end of the growth period.

[Puberty in congenital hypothyroidism (author's transl)]. / La pubertad en el hipotiroidismo congénito.

Puberty was studied in 95 patients with congenital hypothyroidism treated between 1953 and 1977 from the first months or first year of life. Pubertal abnormalities were observed in 13 cases: 1. Delayed puberty in 11 cases (late diagnosis in 6 cases, insufficient treatment in 2 cases, delayed puberty in the family in 1 case). 2. An amenorrhea-galactorrhea syndrome was observed in two cases with insufficient treatment. In the other cases, the outcome of puberty seemed within the normal range. However a careful study showed: 1st. A delay of every stage of puberty, 2nd. The absence of the peak of high velocity in some cases. 3rd. The age of menarche was 13 years 8 months (9 years 1 month-16 years 6 months) (normal girls: 13 years). Final height was dependent upon an early and efficient treatment, and upon a fast catch up of growth and bone maturation.

[Albright's type II osteodystrophy and hypothyroidism due to TSH deficiency. Apropos of a case in a child]. / Ostéodystrophie d'Albright type II et hypothyroidie par déficit en TSH. A propos d'une observation chez l'enfant

The report is dealing with a 10 year-old girl. The diagnosis of Albright's type II osteodystrophy relied on clinical, radiological and biological symptoms: evocative dysmorphic syndrome and absence of disturbances in the phosphocalcic metabolism. Hypothyroidism was secondary to an isolated defect in TSH, and a TRH stimulation test did not induce an increase in plasma TSH.