bluuebunny/crossref_metadata_2025 huggingface dataset:
Decomposing genomic variance using information fromGWA,GWE andeQTLanalysis
Authors: Ehsani A. , Janss L. , Pomp D. , Sørensen P.
Published: December 2015

A commonly used procedure in genome‐wide association (GWA), genome‐wide expression (GWE) and expression quantitative trait locus (eQTL) analyses is based on a bottom‐up experimental approach that attempts to individually associate molecular variants with complex traits. Top‐down modeling of the entire set of genomic data and partitioning of the overall variance into subcomponents may provide further insight into the genetic basis of complex traits. To test this approach, we performed a whole‐genome variance components analysis and partitioned the genomic variance using information fromGWA,GWEandeQTLanalyses of growth‐related traits in a mouse F2population. We characterized the mouse trait genetic architecture by ordering single nucleotide polymorphisms (SNPs) based on theirP‐values and studying the areas under the curve (AUCs). The observed traits were found to have a genomic variance profile that differed significantly from that expected of a trait under an infinitesimal model. This situation was particularly true for both body weight and body fat, for which theAUCs were much higher compared with that of glucose. In addition,SNPs with a high degree of trait‐specific regulatory potential (SNPs associated with subset of transcripts that significantly associated with a specific trait) explained a larger proportion of the genomic variance than didSNPs with high overall regulatory potential (SNPs associated with transcripts using traditionaleQTLanalysis). We introducedAUCmeasures of genomic variance profiles that can be used to quantify relative importance ofSNPs as well as degree of deviation of a trait's inheritance from an infinitesimal model. The shape of the curve aids global understanding of traits: The steeper the left‐hand side of the curve, the fewer the number ofSNPs controlling most of the phenotypic variance.
Frequency of “Time for Self” Is a Significant Predictor of Postnatal Depressive Symptoms: Results from a Prospective Pregnancy Cohort Study
Authors: Woolhouse Hannah , Small Rhonda , Miller Kirsty , Brown Stephanie J.
Published: December 2015

Background

We aimed to explore the relationship between frequency of time for self and maternal depressive symptoms at 6 months postpartum.

Methods

A prospective cohort study of 1,507 first‐time mothers in Australia, recruited in early pregnancy with follow‐up at 6 months postpartum, was conducted. Scores of more than or equal to 13 on the Edinburgh Postnatal Depression Scale were used to identify depressive symptoms.

Results

Of 1,507 women recruited to the study, 92.6 percent completed follow‐up at 6 months postpartum. Almost half (48.5%) reported having time for themselves when someone else looked after their baby (time for self) once a week or more. Compared with women who reported less frequent time for self, women who had time for themselves once a week or more were less likely to report depressive symptoms (unadjusted OR 0.44 [95% CI 0.30–0.66]). Women who had more frequent time for themselves were more likely to have more practical and emotional support. However, this only partially explained the relationship between time for self and depressive symptoms, which remained significant in regression models after adjusting for other recognized risk factors for maternal depression, including social support (adjusted OR 0.60 [95% CI 0.39–0.94]).

Conclusions

Our findings suggest that having time for self at least once a week in the first 6 months after childbirth may have a beneficial influence on maternal mental health. Ensuring women get regular respite from the challenges of caring for a young baby may be a relatively simple and effective way of promoting maternal mental health in the year after childbirth.
I‐branching N‐acetylglucosaminyltransferase regulates prostate cancer invasiveness by enhancing α5β1 integrin signaling
Authors: Mikami Jotaro , Tobisawa Yuki , Yoneyama Tohru , Hatakeyama Shingo , Mori Kazuyuki , Hashimoto Yasuhiro , Koie Takuya , Ohyama Chikara , Fukuda Minoru
Published: December 2015

Cell surface carbohydrates are important for cell migration and invasion of prostate cancer (PCa). Accordingly, the I‐branching N‐acetylglucosaminyltransferase (GCNT2) converts linear i‐antigen to I‐branching glycan, and its expression is associated with breast cancer progression. In the present study, we identified relationships between GCNT2 expression and clinicopathological parameters in patients with PCa. Paraffin‐embedded PCa specimens were immunohistochemically tested for GCNT2 expression, and the roles of GCNT2 in PCa progression were investigated using cell lines with high GCNT2 expression and low GCNT2 expression. GCNT2‐positive cells were significantly lesser in organ‐confined disease than in that with extra‐capsular extensions, and GCNT2‐negative tumors were associated with significantly better prostate‐specific antigen‐free survival compared with GCNT2‐positive tumors. Subsequent functional studies revealed that knockdown of GCNT2 expression in PCa cell lines significantly inhibited cell migration and invasion. GCNT2 regulated the expression of cell surface I‐antigen on the O‐glycan and glycolipid. Moreover, I‐antigen‐bearing glycolipids were subject to α5β1 integrin–fibronectin mediated protein kinase B phosphorylation. In conclusion, GCNT2 expression is closely associated with invasive potential of PCa.
Importance of immunopharmacogenomics in cancer treatment: Patient selection and monitoring for immune checkpoint antibodies
Authors: Choudhury Noura , Nakamura Yusuke
Published: December 2015

In the last 5 years, immune checkpoint antibodies have become established as anticancer agents for various types of cancer. These antibody drugs, namely cytotoxic T‐lymphocyte‐associated antigen, programmed death‐1, and programmed death ligand‐1 antibodies, have revealed relatively high response rates, the ability to induce durable responses, and clinical efficacy in malignancies not previously thought to be susceptible to immune‐based strategies. However, because of its unique mechanisms of activating the host immune system against cancer as well as expensive cost, immune checkpoint blockade faces novel challenges in selecting appropriate patient populations, monitoring clinical responses, and predicting immune adverse events. The development of objective criteria for selecting patient populations that are likely to have benefit from these therapies has been vigorously investigated but still remains unclear. In this review, we describe immune checkpoint inhibition‐specific challenges with patient selection and monitoring, and focus on approaches to remedy these challenges. We also discuss applications of the emerging field of immunopharmacogenomics for guiding selection and monitoring for anti‐immune checkpoint treatment.
Introduction of positron emission tomography into the Western Norwegian Health Region: Regional balance in resource utilization from 2009 to 2014
Authors: Stokmo Henning Langen , Reitan Bernt Christian , Johnsen Boel , Gulati Ankush , Kleven‐Madsen Nina , Adamsen Tom Christian Holm , Biermann Martin
Published: December 2015

Background

The aim was to compare resource utilization across the four health trusts within the Western Norway Regional Health Authority since the establishment of positron emission tomography (PET) at Haukeland University Hospital in Bergen in 2009.

Methods

Metadata from all PET examinations from 2009 to 2014 were automatically imported from the PET centre's central production database into a custom‐developed database system, MDCake. A PET examination was defined as a procedure based on a single injection of radioactive tracer. The patients' place of residence and tentative diagnosis were coded based on the available clinical information.

Results

The total number of PET examinations increased from 293 in 2009 to 1616 in 2014. The number of PET examinations per year increased across all diagnostic groups, but plateaued for lung cancer, gastrointestinal cancer and malignant melanoma since 2013. The number of examinations per capita was evenly distributed between the three northern health trusts with an average of 1260 PET studies per million inhabitants in 2014. However, patients residing in the most southerly health trust received between 44% (2010) and 27% (2014; P<0·001, repeated measures ANOVA) fewer examinations per capita per year.

Conclusion

Centralized PET in the Western Norwegian health region meets the current clinical demand for patients residing in the three northern health trusts while patients from the most southern health trust receive approximately 30% fewer PET examinations. Access to specialized health care should be monitored routinely in order to identify inequalities in referral patterns and resource utilization.
HETEROGENEITY IN STATE‐DEPENDENT UTILITY: EVIDENCE FROM STRATEGIC SURVEYS
Authors: Brown Jeffrey R. , Goda Gopi Shah , McGarry Kathleen
Published: December 2015

A standard result of life‐cycle models under uncertainty is that optimizing individuals equate the expected marginal utility of consumption across states of the world if insurance is available at actuarially fair rates. A small empirical literature has suggested that the marginal utility of consumption is lower in less healthy states. We use a novel survey‐based measure to document significant heterogeneity in health‐state dependence across individuals largely orthogonal to standard controls. We further show that individuals value unhealthy states of the world more when facing work‐limiting disabilities than when facing disabilities requiring long‐term care, and when facing physical rather than mental disabilities. (JEL D12, I10)
Improving care and treatment options for women and girls with bleeding disorders
Authors: Kulkarni Roshni
Published: December 2015

Women and girls may experience increased bleeding symptoms as carriers of haemophilia. They can also be affected by other hereditary bleeding diatheses such as von Willebrand disease, platelet dysfunction defects or deficiencies of coagulation factors (F) such as FI, FII, FV, FVII, FX, FXI and FXIII. In addition to general bleeding symptoms, such disorders pose unique problems for women due to their impact on reproductive health. Women and adolescent girls with undiagnosed bleeding disorders frequently experience heavy menstrual bleeding (HMB; menorrhagia), leading to impairment of daily activities. Other gynaecological and obstetric manifestations, for example miscarriage, bleeding during pregnancy and postpartum haemorrhage (PPH), can occur. Treatment for HMB should consider patient wishes relating to preservation of fertility, and management options include hormonal measures, desmopressin, antifibrinolytics, platelet concentrate transfusions and clotting factor therapy. During pregnancy, monitoring clotting factor levels informs the need for prophylactic therapy; subsequent haemostatic cover can minimise PPH. Under‐recognition of bleeding disorders in females may lead to inappropriate, or lack of, treatment. This may be avoided by increased disease awareness, prompt and accurate diagnosis, and a multidisciplinary approach to patient care. This review considers the range of hereditary bleeding disorders that may affect women and adolescent girls, and their evaluation and management.
Challenges in the management of haemophilia on transition from adolescence to adulthood
Authors: Brand Brigitte , Dunn Spencer , Kulkarni Roshni
Published: December 2015

Patients with haemophilia undergo many transitions during their lives, but the period between adolescence and adulthood is particularly challenging. During this time, the patient must deal with all of the typical biological, social and emotional changes associated with this phase of life, whilst at the same time, adapting his lifestyle to the needs of his condition, transferring from paediatric to adult services and, most importantly, accepting increasing (and ultimately full) responsibility for managing his condition. Parents may also find their diminishing role equally challenging. Perhaps not surprisingly, given the challenges that adolescents face, treatment adherence during this time is generally low, which can lead to recurrent joint bleeds, chronic pain and reduced quality of life. To address the challenges, it is critical that a transition programme is put in place that meets the needs of not only the patient, but also his parents and healthcare providers. Key elements of the plan are a multidisciplinary approach, early planning, patient education and appropriate follow‐up. A successful programme will equip all parties with the skills to deal with the challenges of transition from adolescence to adulthood, ensuring that the benefits of treatment in childhood are maintained, thus optimising health outcomes and quality of life.
Melanin‐Based Coloration Covaries with Hiding and Exploratory Behavior in Male Spanish Terrapins
Authors: Ibáñez Alejandro , Pellitteri‐Rosa Daniele , Sacchi Roberto , López Pilar , Martín José
Published: December 2015

Melanin‐based coloration reflects mostly social status and dominance in males of several species. However, the relation of melanism with other suites of behavioral traits has received less attention. Here, we examined whether the melanic coloration of the shell of male Spanish terrapins Mauremys leprosa was related to several behavioral patterns. To test this, we simulated predatory attacks of different risk levels and measured the time that the turtles spent hiding entirely in their own shells (i.e. appearance times). We also measured the activity level of the turtles in a novel‐environment test. The results showed that melanin‐based coloration was related to antipredatory behavior. Male terrapins with a greater extent of black coloration in their shells demonstrated shorter appearance times after a predator attack. However, this pattern was significant only when turtles were subjected to a high risk. In addition, darker turtles had longer latency times in a novel environment. The results of the present study support the hypothesis that melanin‐based coloration may be associated with some behavioral functions. Our study provides a good framework for future studies concerning the effect of melanin‐coloration on multiple behavioral traits that could be applied to further research using other animal models.
Food Price Uncertainty and Political Conflict
Authors: O'Trakoun John
Published: December 2015

Waves of concurrent, cross‐country political turmoil suggest that global economic forces can serve as a catalyst for intrastate conflict. This article analyses the role of uncertainty shocks to global food commodity prices in generating political conflict in developing countries. I build a simple model to show that shocks to the uncertainty of commodity export prices can elicit civil conflict in a small open economy. Econometric evidence from a cross‐country panel data set documenting intrastate civil conflict and global food commodity prices from 1966–90 lends support to this hypothesis. The results suggest that policies which reduce the uncertainty of export prices faced by food commodity exporters can facilitate political stability in conflict‐vulnerable countries.
Absorption and bioavailability of oral erythromycin.
Authors: Mather LE , Austin KL , Philpot CR , McDonald PJ
Published: December 2015

1 Extent and rate of absorption of erythromycin were studied in 24 healthy volunteers whose disposition kinetics after i.v. injections had been previously documented. 2 Two clinically attractive oral dosage regimens were administered: erythromycin stearate tablets 1 h before meals (Regimen A), and erythromycin base capsules 30 min after start of meals (Regimen B), each equivalent to erythromycin 250 mg, 6 h apart for 9 doses. 3 Serum concentrations of erythromycin measured during the 1st and 9th (steady‐state) dosing intervals resulted in higher maximum serum concentrations for Regimen A (median 1.1, range 0‐3.3 and 2.7, 0.6‐7.3 mg/l for Doses 1 and 9, respectively) compared with Regimen B (0.4, 0‐2.2 and 1.4, 0.2‐4.9 mg/l). 4 Absorption occurred earlier with Regimen A with times to maximum concentrations (median, range) being 128, 60‐greater than 360 and 118, 75‐210 min for doses 1 and 9 respectively, (lag times 75, 15‐ greater than 360 and 73, 10‐110 min) compared with 303, 130‐greater than 360 and 173, 45‐greater than 360 min (lag times 183, 70‐greater than 360 and 190, 20‐330 min) for Regimen B. 5 Where it could be assessed, absolute bioavailability for Regimen A was approximately 30% (Dose 1) and 65% (Dose 9) and 40% for both doses of Regimen B. 6 Whereas individual serum concentration‐time curves were accurately predicted by the mean for Regimen A, predictability for Regimen B was impossible due to prolonged and variable lag time. 7 The large intersubject variability in erythromycin serum concentration after oral administration, has been shown conclusively to be related to variability in absorption kinetics and absolute bioavailability rather than to variability in disposition kinetics.
Influence of environmental temperature and humidity on bronchial responses during assessment of selectivity of beta‐adrenoceptor antagonists in man.
Authors: Taylor EA , Trembath PW , Warrington SJ
Published: December 2015

1 The effects of beta‐adrenoceptor antagonists given intravenously in single doses were examined in a double‐blind, placebo controlled study performed in six healthy volunteers. Heart rate and peak expiratory flow rate (PEFR) were measured at rest and during standardised exercise. 2 Atenolol 0.2 mg/kg, betaxolol 0.15 mg/kg, practolol 1 mg/kg and propranolol 0.2 mg/kg all reduced heart rate to a similar extent during exercise at 2 and 4 h after administration; betaxolol 0.6 mg/kg had a significantly greater effect than the other treatments at all times. Only betaxolol 0.15 and 0.6 mg/kg significantly inhibited exercise tachycardia at 24 h. 3 None of the treatments studied had any effect on PEFR at rest or during exercise. 4 A second study was performed to determine whether this lack of effect of propranolol on exercise PEFR could have been due to the warm and humid conditions prevailing during the experiment. Eight healthy men underwent a standardised exercise test under alternately ‘warm and humid’ and ‘cool and dry’ conditions before and after propranolol 0.2 mg/kg or saline placebo intravenously. 5 Propranolol treatment did not influence resting or exercise PEFR in either environment, but did reduce FEV1 immediately after exercise under the cool and dry conditions but not under the warm and humid conditions. 6 Comparison of the effects of beta‐adrenoceptor antagonists on exercise heart rate and PEFR is not a reliable or sensitive method of measuring the cardioselectivity of these drugs. 7 Environmental temperature and humidity should ideally be controlled when the action of any drug on airflow resistance is being studied.
Male Agonistic Behaviour of the Bushcricket Mygalopsis marki Bailey in Response to Conspecific Song (Orthoptera: Tettigoniidae)
Authors: Dadour Ian R. , Bailey Winston J.
Published: December 2015

Experiments were conducted on Mygalopsis marki Bailey to determine the response of calling males to singing intruders. By increasing the density of natural aggregations of singing males we were able to observe the behavioural responses of individuals. In high density situations, males sang from lower perches in their plant and this effect was correlated with each male's proximity to other calling males. Furthermore, to examine if resident males were affected by conspecific song, a playback technique was employed using tape recordings of M. marki song. The design of the experiment was such that when confronted with an intruder, steadily increasing the intensity of its song, resident males moved to a lower position in the plant and ceased singing.
Individual Variability in the Migratory Orientation of the Savannah Sparrow, Passerculus sandwichensis
Authors: Moore Frank R.
Published: December 2015

Abstract and Summary

Variability characterizes the orientation of migratory birds much as it does other aspects of their behavior. Yet, in most orientation experiments measures of central tendency are emphasized, while existing individual variability is seldom addressed other than to make special statistical effort to reduce it. Massing individuals is only useful, however, if there are insignificant differences among them. When the behavior of individual migrants was monitored over several nights and then compared, individual directional preferences were evident. Among‐individual variability in compass orientation was greater than within‐individual variability. The statistical variation that exists around a group mean seems to be a function of differences among individuals showing rather specific preferences. Because the samples may have consisted of individuals representing different breeding localities, the observed differences among individuals may reflect different migratory goals.

Untersucht wurde an der Grasammer (Passerculus sandwichensis) die Variabilität sowohl innerhalb einer Gruppe als auch am einzelnen Vogel auf dem Frühjahrszug. Mittelwerte für die Gruppe zeigten jahreszeitlich angemessene nördliche Orientierung für jede Versuchsgruppe. Das Verhalten einzelner Zugvögel durch mehrere Nächte ließ individuelle Unterschiede erkennen. Variabilität innerhalb der Gruppe war ausgeprägter als im Verhalten des einzelnen Vogels. Die statistische Abweichung vom Gruppenmittelwert ist allem Anschein nach eine Funktion der Unterschiede zwischen einzelnen Vögeln, die ganz bestimmte Richtungen bevorzugen. Da beide Versuchsgruppen vermutlich aus Vögeln bestanden, die geographisch verschiedenen Populationen mit entsprechend verschiedenen Brutgebieten angehörten, ist es möglich, daß die beobachteten Unterschiede zwischen einzelnen Vögeln auf unterschiedlichen Zugzielen beruhen.
Elective Cesarean Birth: Issues and Ethics of an Informed Decision
Authors: McFarlin Barbara L.
Published: December 2015

Is elective cesarean birth an issue of a woman's autonomy to choose her mode of birth or fear of labor by both the patient and the providers? Are women consenting to this procedure truly informed about the short‐term and long‐term risks associated with cesarean birth versus vaginal birth? This article examines the issues associated with elective cesarean birth and the factors that have led to recent consideration of this option. It is essential that we evaluate how risks, benefits, and liability issues impact the recommendations for the mode of birth. The ethics of making an informed choice as well as ethical professional responsibilities are explored.
Increased NK Activity Is Responsible for Higher Cytotoxicity to HEF Cells by Lymphocytes of Women With Threatened Preterm Delivery
Authors: SZEKERES‐BARTHO JULIA , HADNAGY J. , CSERNUS V. , BALÉZS L. , MAGYARLAKI T. , PACSA A.S.
Published: December 2015

ABSTRACT: Recently we have shown that lymphocytes of pregnant women with threatened preterm delivery (risk group) exerted significantly higher cytotoxic activity to human embryonic fibroblast (HEF) cells than those of healthy pregnant women.

The purpose of this study was to get information on the mechanism of this cytotoxicity. The possibility of prior sensitization to embryonic antigen was excluded, since no difference could be demonstrated between cytotoxic activity of lymphocytes obtained from women with two or more previous pregnancies and that of lymphocytes from never‐pregnant women. For determining the effector cell type responsible for cytotoxicity, lymphocytes of 50 healthy pregnant women and those of 50 risk patients were tested in different cytotoxicity tests using HEF and K‐.562 target cells.

The proportion of NK cells among lymphocytes was determined by counting large granular lymphocytes (LGL), IgG Fc receptor bearing cells, and cells positively stained by NK specific monoclonal antibody. Though no difference in the proportion of NK cells between the two groups was found, risk patients' lymphocytes were significantly more cytotoxic to K‐562 target cells than those of healthy pregnant women. Investigations at the single‐cell level made it obvious that this higher cytotoxic activity originated from increased target cell lysing ability of their lymphocytes, while their conjugating capacity did not differ significantly from that of lymphocytes obtained from healthy pregnant women. Staining conjugates with monoclonal antibodies showed that NK cells were concentrated on the surface of both HEF and K‐.562 cells, so it seems likely that NK activity is responsible for the cytotoxic activity of pregnancy lymphocytes to HEV cells.
Radioautographic Analysis of Surface Markers on Decidual Cells Shared by Cells of the Lymphomyeloid Tissues
Authors: KEARNS MARY , LALA PEEYUSH K.
Published: December 2015

ABSTRACT: Stromal type decidual cells recovered from the murine decidua by a mild collagenase dispersion procedure contain immunoregulatory cells whose ultimate precursors may originate from the bone marrow. To explore the familial relationship of these cells with other cells of the immune system, a battery of cell surface markers recognized on lymphomyeloid cells were examined and quantitated at the morphological level on typical stromal type decidual cells of the dispersed CBA mouse decidua at 8–14 days of syngeneic pregnancy, using a sensitive radioautographic technique. Cells were either labeled directly by exposure to 125I‐labeled monoclonal antibodies against Thy‐1, Mac‐1, or Lyt antigens or indirectly by a sequential exposure to monoclonal anti‐I‐Ak (Ia. 17) or monospecific anti‐I‐Jk antibodies and 125I‐labeled Protein A. Decidual cells were found to be Thy‐1± (13–73% positive, the incidence rising with advancing gestation in the decidua basalis), Mac‐1 ± (present on 6–11% on day 8 and 17–32% on day 12), I‐A−, 1‐J−, and Lyt−. Macrophages within the decidua were Thy‐1−, Lyt−, Mac‐1 +, and I‐A± (present on 5–61% of cells, the incidence rising with advancing gestation). These surface properties of decidual cells along with the presence of FcR, an absence of C3R, and the presence of a unique marker Dec‐1 reported by us earlier, distinguish them from most other stromal type immunoregulatory cells such as Langerhans cells (I‐A+, FcR+, C3R+, Mac‐1−, Thy‐1−), follicular dendritic cells (I‐A+, FcR+, Thy‐1−, Mac‐1−, Dec‐1−), and dendritic reticular cells (I‐A+, FcR−, C3R−, Thy‐1−, Lyt−, Mac‐1). However, a substantial subpopulation of decidual cells share a few properties (1‐A−,Thy‐1+) with another marrow derived stromal type cell in the epidermis termed as epidermal dendritic cells that remain to be investigated for other surface markers such as Mac‐1, Dec‐1, and FcR.
Human Fetal/Neonatal Suppressor Activity: Relation Between OKT Phenotypes and Sensitivity to Prostaglandin E2 in Maternal and Neonatal Lymphocytes
Authors: PAPADOGIANNAKIS NIKOS , JOHNSEN SVEND‐AAGE , OLDING LARS B.
Published: December 2015

ABSTRACT: T lymphocytes from human fetuses and newborns strongly and spontaneously suppress various adult cell functions (i.e. T‐cell proliferation, B‐cell differentiation, and Ig synthesis). The precise phenotype of the suppressor cell is controversial. In this investigation we use cord T‐cell subsets negatively selected by the panning technique or by complement‐mediated lysis using the monoclonal antibodies OKT4 and OKT8. Cord T cells deprived of the OKT4+ subpopulation exerted only a marginal suppressor activity (12 ± 7 as compared to 73 ± 4% of unfractionated T cells) on the proliferation of maternal cells in our PHA‐stimulated co‐culture assay using sex chromosomes as markers for dividing cord (male) and maternal cells. The suppressive effect was direct, i.e. not mediated by induction of maternal OKT8+ suppressor effector cells. Cord and maternal T‐cell subsets were also tested for their sensitivity to exogenous prostaglandin E2 (PGE2) at doses varying between 1.4 × 10−5 and 1.4 × 10−9 M. Both maternal OKT4− and OKT8− T‐cell subsets were highly sensitive to suppression by PGE2. In contrast, cord OKT8− T cells were essentially nonsensitive at all doses of PGE2 used, whereas cord OKT4− T cells were significantly suppressed at four out of five concentrations tested (1.4 × 10−6 through 1.4 × 10−9). Our results suggest a direct correlation between the phenotypes of the cord‐suppressor and maternal‐target T cells and their sensitivity to PGE2.
Antibody Responses in Secondary Aborting Women: Effect of Inhibitors in Blood
Authors: McINTYRE JOHN A. , FAULK W. PAGE
Published: December 2015

ABSTRACT:The perpetually high antipaternal and cell panel antibody reactivity in the blood of secondary aborting patients sets them apart from most multi‐gravid or multiparous women. Our studies with secondary aborters' sera have shown their complement‐dependent cytotoxicity (CDC) reactivity to be abolished by heat treatment (56°C for 30 min) or by solid phase heparin absorptions. This is only observed if treated serum is present; a wash step restores optimal CDC activity. Thus, something in their treated serum not associated with antibody‐binding to target cells is inhibiting CDC activity. A similar inhibitor was found in all human sera tested. Anticomplementary effects were excluded by showing that CDC with horse antihuman leukocyte antibody was not affected by these inhibitors. To investigate this inhibition, we designed a hemagglutination assay (HA) employing rabbit IgG‐coated sheep erythrocytes and human rheumatoid factor. The results of these studies show the presence of an inhibitor (I) to both CDC and HA in normal plasma and serum. Of special interest was the presence of a heat‐labile inhibitor of the inhibitor (I/I) in plasma, but not in serum. Biochemical characterization of the I is in progress. The I/I in plasma appears to be factor V of the clotting system. These observations represent a link between the immune system and clotting mechanisms, which may be important in understanding the pathophysiology of secondary abortion.
Hypothesis: Blocking Factors and Human Pregnancy: An Alternative Explanation for the Success of Lymphocyte Transfusion Therapy in Abortion‐Prone Women
Authors: DAVIES MARTIN
Published: December 2015

ABSTRACT: Recent evidence has demonstrated that the non‐specific immunosuppression that develops during pregnancy is not due to the de novo synthesis of immunosuppressive factors (ISF) but is a result of the activation of pre‐existing molecules. The latter are present in normal sera as inactive complexes with a molecule which is specifically depleted following conception resulting in the activation of the ISF; the depleted molecule is termed the pregnancy‐depleted immunoregulatory factor (pdIRF). Since non‐specific ISF are detected in various diseases, it is proposed that the ISF‐pdIRF relationship observed in pregnancy is a universal phenomenon and that the depletion of pdIRF and the activation of ISF can be achieved by a variety of stimuli. It is further proposed that abortion‐prone women fail to adequately deplete their pdIRF levels so that the ISF are not activated. However, owing to the universal nature of the system, lymphocyte transfusion therapy supplies the necessary stimuli so that the pdIRF levels are depleted and the ISF activated which ensures a successful outcome to the pregnancy.
Presence of an Endothelial Antigen on the Syncytiotrophoblast of Human Chorionic Villi: Detection by a Monoclonal Antibody
Authors: VOLAND JOSEPH R. , FRISMAN DENNIS M. , BAIRD STEPHEN M.
Published: December 2015

ABSTRACT: We describe a monoclonal antibody, B721. This antibody reacts with an antigen present on vascular endothelium and on the syncytiotrophoblast of term chorionic villi. The antigen is absent from the trophoblast of the chorion, from the amniotic epithelium, and from normal peripheral blood or lymph node lymphocytes. We discuss the possible functional roles of the antigen. We propose that the syncytiotrophoblast, by expressing endothelial antigens, mimics endothelium and may perform endothelial functions.
The Effect of Maternal Antigenic Stimulation Upon the Active Immune Responsiveness of Their Offspring: Suppression Induced by Soluble Protein Antigen, Ovalbumin, in Mice
Authors: IWATA ICHIRO , SHIMIZU SHOJI , YAMAGUCHI NOBUO
Published: December 2015

ABSTRACT: The active immune responsiveness of the offspring of pregnant mice stimulated with heterologous protein antigen was investigated by measuring the plaque‐forming cells (PFC). Mice (C57BL/10;B10) immunized once in pregnancy with ovalbumin (OVA) in the form of Al(OH)3 gel (in alum) or in a soluble form (in saline) developed no anti‐OVA PFC response. The anti‐OVA PFC response suppression induced in the offspring was high in the offspring of alum‐treated mothers and low in those of saline‐treated mothers. The optimal dose of OVA in alum that induces the highest immunological memory in pregnant mice caused the complete suppression of PFC development in their offspring. The same dose of OVA in saline induced a negative immunological memory in pregnant mice and partial suppression in the offspring. On the other hand, mice primed prior to conception and boosted during pregnancy developed anti‐OVA PFC in significant numbers, and only a partial suppression was established in their young. Based on these data, we discussed the possible mechanisms concerned with the specific suppression induced in the young B10 mice stimulated by OVA.
Distribution of Trop 3 and 4 Antigens as Defined by Monoclonal Antibodies Raised Against a Human Choriocarcinoma Cell Line
Authors: SOUBIRAN PIERRE , HSI BAE‐LI , LIPINSKI MARC , YEH CHANG‐JING G. , VAIGOT PIERRE , MASSEYEFF RENE
Published: December 2015

ABSTRACT: The reactivities of Trop 3 and 4 monoclonal antibodies (MAbs) were studied on human term and 7‐week extraembryonic membranes, adult tissues, and cell lines. Trop 3 MAb reacted with cells of chorionic villi, decidua, amniotic epithelium, and basal plate trophoblast. Trop 4 MAb reacted only with syncytiotrophoblast. On epithelium, Trop 3 MAb bound to stratified and glandular epithelium, but Trop 4 MAb reactivity was limited to basal keratinocytes. On peripheral blood mononuclear cells, Trop 3 MAb reacted with the majority of cells and Trop 4 MAb with the totality. Most cell lines were positive with both MAbs. However, one chemically induced MHC mutant was negative and another decreased its expression of Trop 3 antigen. Our results suggest Trop 3 MAb might recognize a monomorphic determinant of TLX antigens and Trop 4 is involved in cell proliferation or in cell‐to‐cell interaction.
An Improved Immunobead Test Procedure for Detecting Sperm Antibodies in Serum
Authors: CLARKE G.N.
Published: December 2015

ABSTRACT: In order to improve the efficiency of IBT screening of sera for sperm antibodies, the use of immunobeads with attached rabbit antibodies directed against whole human immunoglobulin (IBT‐GAM) was investigated and compared with the use of separate immunobeads specific for each of the main immunoglobulin classes (IBT‐IgG, IBT‐IgA, IBT‐IgM). Sera found positive by the IBT‐GAM procedure were then tested by IBT‐IgG, ‐IgA, and ‐IgM procedures to determine the immunoglobulin class or classes of the sperm antibody. The new procedure is much more efficient for screening larger batches of sera and gives results identical with those from the old procedure when ≥50% sperm coating is used as criterion of positivity. We now use the IBT‐GAM procedure for initial screening of all sera, followed by further testing of positive sera on the same preparation to determine the immunoglobulin class or classes of the antibody.
Cesarean Section Prophylaxis: Comparison of Two Doses With Three Doses of Mezlocillin
Authors: CROMBLEHOLME WILLIAM R. , GREEN JAMES R. , OHM‐SMITH MARILYN , DAHROUGE DONNA , DEKAY VICKI , RIDEOUT ANNE , SWEET RICHARD L.
Published: December 2015

ABSTRACT: A prospective randomized double‐blind comparison of two doses, with three doses of mezlocillin for nonelective cesarean section prophylaxis was performed. One hundred seven (107) patients were evaluated. Mezlocillin (4 g) was given post‐cord clamping and then at 4‐h intervals for a total of two doses or three doses. The incidence of febrile morbidity was lower in the three‐dose group (2 of 46, 4%) than the two‐dose group (14 of 61, 23%) (P<0.02). However, the incidence of infectious morbidity was not different between the three‐dose group (3 of 46, 7%) and the two‐dose group (10 of 61, 16%), and the incidence of endomyometritis was similar in the two groups (6.5% vs 9.8%). Among failures of prophylaxis there were no differences compared to successes in the number of potential commensals or potential pathogens cultured from amniotic fluid. However, the proportion of failures among patients with both commensals and potential pathogens isolated (10/58) was significantly greater than among patients with none or only commensals isolated (1/37) (P<0.03). We found mezlocillin to be an effective agent for perioperative cesarean section prophylaxis with two doses as effective as three doses. The presence of clinically important organisms in the amniotic fluid at the time of operation typified patients with postoperative infectious complications despite perioperative prophylaxis.
Monoclonal Antibody Defined Phenotypes of Peripheral Blood Lymphocytes in Cancer of the Uterine Cervix
Authors: PILLAI M. RADHAKRISHNA , BALARAM PRABHA , PADMANABHAN T.K. , NAIR M. KRISHNAN
Published: December 2015

ABSTRACT: Immunological phenotypes of lymphocytes from peripheral blood of 100 patients with different stages and histologies of cancer of the uterine cervix were analyzed using monoclonal antibodies and F(ab)2fragments of antihuman immunoglobulin. The T lymphocyte population was decreased in advanced cases of the cancer along with a rise in the B cell numbers. The OKT4+ cells generally showed a decrease in the cancer patients in contrast to the increase shown by the OKT8+ cells. The OKT4/OKT8 ratio was altered in this cancer except in patients with stages I and IIA. In terms of histology, the poorly differentiated tumors showed a higher imbalance of the cellular composition when compared to the well‐differentiated and moderately differentiated tumor‐bearing patients. These findings point toward a possible alteration in the immune effector cells of these cancer‐bearing patients.
Indirect Mixed Antiglobulin Reaction (MAR) as a Screening Procedure for Antisperm Antibodies. II. Clinical Studies
Authors: MEINERTZ HELLE
Published: December 2015

ABSTRACT: In this study the question was raised whether the indirect mixed antiglobulin reaction (MAR) using donor spermatozoa could substitute the direct MAR requiring motile spermatozoa in the patient's ejaculate in the screening for antisperm antibodies.

Serum and seminal plasma from 48 men selected on the basis of the results in the direct MAR were tested by the indirect MAR. Both tests were carried out for IgG and IgA antisperm antibodies.

A statistically significant correlation was found both between the sperm‐bound IgG and the free IgG antisperm antibodies in serum as well as in seminal plasma and between sperm‐bound IgA and the free IgA antisperm antibodies in seminal plasma whereas no correlation was found between the sperm‐bound IgA and the free IgA antisperm antibodies in serum. This finding strongly supports the concept that the major part of the IgA antisperm antibodies in the ejaculate are locally produced.
Isolation and Characterization of Rat Trophoblast Cells
Authors: WANG KUAN‐I , HO G‐NERNG , MISRA DHIRENDRA N. , KUNZ HEINZ W. , GILL THOMAS J.
Published: December 2015

ABSTRACT: Previous immunohistochemical studies of the rat placenta using specific alloantisera and/or monoclonal antibodies showed that the basal zone trophoblasts stained for Pa and Aa class I major histocompatibility complex (MHC) antigens and for the human SP1‐related antigen. In an effort to isolate the basal zone trophoblast cells from the rat placenta, we used these markers to assess the degree of purification of the cells separated by density gradient centrifugation using either Ficoll‐Hypaque or Percoll as the gradient medium. The cells were put either on the top or at the bottom of discontinuous density gradients in the range of 1.005‐1.10 or/ml. The cell separation profiles for the two media were different. With Percoll, most of the trophoblast cells (80–95%) were collected at the density gradients 1.04/1.06 and 1.06/1.08, whereas with Ficoll‐Hypaque, these gradients separated only a small fraction (4–23%) of the trophoblast cells, and most of them pelleted at the bottom of the tube. The trophoblast cells separated by Ficoll‐Hypaque, however, showed fewer contaminant cells than those separated by the Percoll gradients.
Histocompatibility Antigens and Habitual Abortion
Authors: CAUCHI M.N. , TAIT B. , WILSHIRE M.I. , KOH S.H. , MRAZ G. , KLOSS M. , PEPPERELL R.
Published: December 2015

ABSTRACT: Eighty‐five couples with habitual abortion were studied: 43 were primary aborters (i.e., had no advanced pregnancy beyond 20 weeks gestation), and 42 were secondary aborters. The only significant finding in primary female aborters was a reduction in the incidence of B35. In contrast, in secondary female aborters there was a reduction in the incidence of DR3 and A1/ B8/DR3 and an increase in the degree of homozygosity of HLA B. In the male partners of primary aborters, there was a reduced incidence of DR3 and A1/B8/DR3. In addition, in male partners of both primary and secondary aborters, there was increased HLA‐B homozygosity and increased frequency of DR4‐5 phenotype. Increased sharing of HLA antigens between partners was not found to be significantly different from the control population.

These findings emphasize that primary and secondary female aborters form distinct populations, which could explain differences in immunological responses to various antigens, including fetal‐related antigens. The closely related findings in female secondary aborters and male partners of primary aborters are intriguing but cannot be explained. Whether or not these genetic markers bear any relationship to reproductive success remains to be determined.
Suicide Risk Factors In Alcohol Abuse
Authors: Motto Jerome A.
Published: December 2015

ABSTRACT: The “clinical model” approach to estimating suicide risk assumes that persons sharing specific attributes will also share certain indicators of vulnerability to suicide. This would warrant an empirically derived risk assessment scale applicable only to persons with those attributes. Nine hundred seventy eight persons at risk for suicide who met our criteria for alcohol abuse were interviewed at length and followed for two years, during which 53 (5.5 percent) committed suicide. Eleven variables which best differentiated those who suicided from those who did not in an index set were then applied to an independent validation set. Clinical implications of the findings are discussed.
Homicide Prevention and Intervention
Authors: Allen Nancy H.
Published: December 2015

ABSTRACT: Homicide is defined a major public health problem, as well as a criminal justice problem. The direct implications of suicidology theory for the understanding and prevention of homicide are discussed. Specifically mentioned are the concepts of prevention‐intervention‐postvention; clues; lethality; the identification of high risk groups; and the psychological autopsy. The need for homicide‐prevention education is explored at levels ranging from a better informed public to more knowledgeable professionals.
Strategies for Suicide Intervention by Telephone
Authors: Hinson Jennifer
Published: December 2015

ABSTRACT: Within the authoritative role, the telephone counselor engages the caller in realistic talk of dying in an effort to reinstate control. Anxiety reduction is accomplished through problem clarification. Narrowing down open negative statements reduces diffuse anxiety, while reinterpreting events reduces energized anxiety. To provide hope, care can be proven as genuine implicitly by using the caller's name, filling conversation with emotive gestures, and extending “why” questions. Explicit proof can be in the form of active listening, tolerance of dispositions, and involvement such as suggesting milk, tissues, or calling on significant others. To further provide hope and to reinstate control, allowance is given for manipulation such as the caller setting the initial mood of conversation. A model is presented for pursuing alternatives and a technique of interrogative restating to broaden resources. Time‐outs are posited for stymied intervention, detective work for discovering critical information, and guilt inducement as a means of recourse. To close the call, promises are extracted from and reinforcement statements are administered to the caller.
Suicide Epidemics and Newspaper Reporting
Authors: Littmann Sebastian K.
Published: December 2015

ABSTRACT: This paper looks at the relationship between suicide‐related newspaper reports and a subway‐suicide epidemic. More reports were published during the epidemic, without statistically significant differences between epidemic and nonepidemic years. There did not appear to be an excess of reports antecedent to the suicide. The role of newspapers is discussed with particular reference to suicide epidemics. The need for studies of content of newspaper items related to self‐harm is emphasized.
Preliminary Field‐Testing of a Risk Estimator For Suicide
Authors: Motto Jerome A.
Published: December 2015

ABSTRACT: A 15‐item suicide risk estimator, empirically derived from a prospective study of 2, 753 suicidal persons, was given a field trial in five clinical settings. Two hundred ninety subjects were included. Volunteer crisis workers needed an average of 4.5 minutes to complete the instrument, and rated its ease of administration 2.5 on a 5‐point scale. When compared with clinical ratings, the instrument estimated suicide risk slightly higher than did the interviewers. Scale items that differed from the raters' intuition tended to be omitted more than others. The trial provided valuable information needed to prepare for a large scale evaluation.
An Empirical Investigation of Shneidman's Formulations Regarding Suicide
Authors: Leenaars Antoon A. , Balance William D. G. , Wenckstern Susanne , Rudzinski Donald J.
Published: December 2015

ABSTRACT: This study of suicide notes involved the deduction of 50 protocol sentences that reflected important aspects of Shneidman's formulations regarding suicide. Independent judges noted the incidence of contents corresponding to the protocol sentences in 33 genuine and 33 simulated notes. Statements that were found significantly and more frequently in genuine notes included the following: the experience of adult trauma such as a calamitous relationship; a rejection; the withdrawal of a significant person resulting in despair; perceiving another as dooming one to the suicide; expressions of ambivalence; feelings of love, hate and other emotions; feelings of helplessness, pessimism and emotional confusion; appearing to be intoxicated by one's overpowering emotions and constricted perceptions; and the communications appearing to have unconscious implications. Statements of “egression” and more logical reasoning were more characteristic of the simulated notes. A frequency count in the genuine notes indicated that many protocol sentences were also very predictive of the content. Implications of the results are discussed.
On the Alleged Ineffability of Death
Authors: Mayo David
Published: December 2015

ABSTRACT: A number of recent theorists, all proceeding on the assumption that there is no afterlife, argue that the notion of one's own death defies comprehension in ways that have important implications. Some argue this “ineffability” of death precludes a rational decision to die. Dr. Edwin Shneidman maintains that it makes the notion of our own death unintelligible to each of us. In this paper, these arguments are criticized. It is maintained that death is not so inscrutible as these theorists would have us believe.