bluuebunny/crossref_metadata_2025 huggingface dataset:
Updates from guardian™: a comprehensive registration programme
Authors: Ozelo Margareth C.
Published: December 2015

Turoctocog alfa is an approved B‐domain truncated recombinant factor VIII concentrate for adults and children with haemophilia A. Clinical data for turoctocog alfa have been reported from the guardian™1, guardian™2 and guardian™3 phase III trials. guardian™1 and guardian™3 phase III trials enrolled 150 adolescents/adults (≥12 yr), and 63 children (<12 yr), respectively, with previously treated severe haemophilia A and no history of inhibitors; 188 of these patients continued into the ongoing guardian™2 extension trial. In the three trials, patients have received prophylaxis with turoctocog alfa three times weekly or every second day, with breakthrough bleeds resolved to an expected postinjection level of ≥0.50 IU/mL. No safety concerns have arisen, and no patients have developed confirmed inhibitors (primary endpoint). Indeed, no confirmed inhibitors have been detected in >200 patients treated for a cumulative total of >54 000 exposure days in the phase III trials. Pooled efficacy data show a favourable long‐term effect of turoctocog alfa on annualised bleeding rate and a success rate for haemostatic response of 86%; 90% of bleeds were resolved with 1–2 doses. This article reviews the clinical development of turoctocog alfa with reference to the guardian™ clinical programme, describing results obtained to date and ongoing trials.
Short‐ and long‐term surgical outcomes of temporal lobe epilepsy associated with hippocampal sclerosis: Relationships with neuropathology
Authors: Deleo Francesco , Garbelli Rita , Milesi Gloria , Gozzo Francesca , Bramerio Manuela , Villani Flavio , Cardinale Francesco , Tringali Giovanni , Spreafico Roberto , Tassi Laura
Published: December 2015

Objective

Hippocampal sclerosis (HS) is the most frequent neuropathologic finding in patients undergoing surgery for intractable temporal lobe epilepsy (TLE). The International League Against Epilepsy (ILAE) has recently proposed a new classification of HS based on specific patterns of cell loss. The aim of this study was to investigate the relationships between HS types, their etiologic factors, and the short‐ and long‐term postsurgical outcomes of patients undergoing surgery because of drug‐resistant TLE with HS.

Methods

Two hundred thirteen patients with a neuropathologic diagnosis of HS and a minimum follow‐up of 2 years were divided on the basis of their ILAE HS type and further classified into: (1) isolated HS, (2) HS associated with focal cortical dysplasia (FCD IIIa), or (3) HS associated with other lesions. Their clinical and neuropathologic data were correlated with their Engel class postsurgical outcomes.

Results

The main findings were the following: (1) HS type 1 was associated with a longer duration of epilepsy; (2) >80% of the patients had an Engel class I short‐ and long‐term outcomes, regardless of HS type and associated pathology; (3) short‐ and long‐term postsurgical outcomes were less satisfactory in the patients who were completely seizure‐free (Engel class Ia), and patients with HS type 2 had better long‐term seizure outcomes than those with type 1; (4) the concomitant presence of FCD contributed to a worse outcome, regardless of HS type; and (5) a shorter duration of epilepsy significantly correlated with an Engel class Ia outcome.

Significance

These data suggest that HS type and associated pathologies may predict the risk of recurrence, but other variables such as the duration of epilepsy need to be considered. A common neuropathologic classification system may help to identify preoperative predictive factors and improve the selection of patients who may benefit from epilepsy surgery.
Juvenile Collared Lizards Adjust Tail Display Frequency in Response to Variable Predatory Threat
Authors: York Joshua R. , Baird Troy A.
Published: December 2015

Antipredator behavioral tactics have evolved in phylogenetically diverse animal clades and often involve prey initiating conspicuous display patterns when encountering potential predators. Using detailed behavioral observations in the field, we report the first description of conspicuous tail displays in juvenile collared lizards (Crotaphytus collaris), a species that does not have tail autotomy. When approached in the field, lizards gave four stereotypical displays involving the tail, suggesting that these might function as antipredator signals. To test this hypothesis, we compared the frequency of tail displays given by juveniles during approach experiments relative to control trials involving observation from afar. We then further manipulated the intensity (low threat, high threat) with which we threatened lizards by varying our angle of approach relative to the body‐axis orientation of lizards resting on a perch sloping away from the observer. Our results show that juveniles consistently performed all four types of tail displays in response to our approaches, but subjects never displayed during non‐threat control trials. Moreover, lizards were more likely to remain emergent and give tail displays when we approached them head‐on with their bodies sloping away (low threat), but were more likely to take refuge when approached from the side and behind (high threat). The positive relationship between the frequency of display and risk level suggests that tail displays function to signal that juvenile lizards have detected potential predators, which may deter further pursuit. Together, our results provide the first account of visual displays involving the tail in collared lizards and suggest that these displays function to signal potential predators.
Epistatic partners of neurogenic genes modulate Drosophila olfactory behavior
Authors: He X. , Zhou S. , St. Armour G. E. , Mackay T. F. C. , Anholt R. R. H.
Published: December 2015

The extent to which epistasis affects the genetic architecture of complex traits is difficult to quantify, and identifying variants in natural populations with epistatic interactions is challenging. Previous studies in Drosophila implicated extensive epistasis between variants in genes that affect neural connectivity and contribute to natural variation in olfactory response to benzaldehyde. In this study, we implemented a powerful screen to quantify the extent of epistasis as well as identify candidate interacting variants using 203 inbred wild‐derived lines with sequenced genomes of the Drosophila melanogaster Genetic Reference Panel (DGRP). We crossed the DGRP lines to P[GT1]‐element insertion mutants in Sema‐5c and neuralized (neur), two neurodevelopmental loci which affect olfactory behavior, and to their coisogenic wild‐type control. We observed significant variation in olfactory responses to benzaldehyde among F1 genotypes and for the DGRP line by mutant genotype interactions for both loci, showing extensive nonadditive genetic variation. We performed genome‐wide association analyses to identify the candidate modifier loci. None of these polymorphisms were in or near the focal genes; therefore, epistasis is the cause of the nonadditive genetic variance. Candidate genes could be placed in interaction networks. Several candidate modifiers are associated with neural development. Analyses of mutants of candidate epistatic partners with neur (merry‐go‐round (mgr), prospero (pros), CG10098, Alhambra (Alh) and CG12535) and Sema‐5c (CG42540 and bruchpilot (brp)) showed aberrant olfactory responses compared with coisogenic controls. Thus, integrating genome‐wide analyses of natural variants with mutations at defined genomic locations in a common coisogenic background can unmask specific epistatic modifiers of behavioral phenotypes.
Silage fermentation profile, chemical composition and economic evaluation of millet and soya bean grown in monocultures and as intercrops
Authors: Jahanzad E. , Sadeghpour A. , Hashemi M. , Keshavarz Afshar R. , Hosseini M. B. , Barker A. V.
Published: December 2015

In recent years, dairy farmers in semi‐arid regions have shifted from maize (Zea mays L.) as their primary source of feed to drought‐tolerant crops, such as millet (Pennisetum glaucum L.), due to lack of water for irrigation. However, millet alone may not provide feed of sufficient quality and crude protein content for dairy cows. A field experiment was conducted in 2 years to evaluate (i) whether intercropping millet with a relatively drought‐tolerant soya bean cultivar (Glycine max Merr, cv. Williams) could improve silage quality with minimum yield penalty, and (ii) if the application of molasses could further enhance the nutritive value of silage of millet–soya bean intercrops. There were three intercropping ratios (60% millet with 40% soya bean, 50% millet with 50% soya bean, 40% millet with 60% soya bean) and monocultures of millet and soya bean. Mixed forages were treated with three levels of molasses: M0 (without molasses), M1, and M2 (2·5 and 5% fresh matter respectively). Inclusion of soya bean in millet crops resulted in decreased silage yield compared with millet alone. The highest yield was obtained from the ratio of 60% millet with 40% soya bean. Molasses‐treated silage had higher lactic acid, lower pH, and lower acid detergent fibre (ADF) and neutral detergent fibre (NDF). Silage produced from millet–soya bean intercrops exhibited enhanced fermentation, indicated by lower pH (3·64) and higher lactic acid (16·63 g kg−1 DM) than silage from monocultures. Intercropping ratios had lower water‐soluble carbohydrate, ADF and NDF than millet monoculture. Overall, an intercropping ratio of 60% millet with 40% soya bean was advantageous over other ratios in terms of higher yield, nutritive value and economic value.
Effects of Extrusion Processing Factors on Reliability of Ceramic Packed Bed Applied for Chemical Contactors
Authors: Salem Amin
Published: December 2015

The fracture behaviors of three ceramic categories were studied to achieve the appropriate conditions for manufacturing reliable packed bed employed in liquid–gas contactors. The compression strength of beds was measured by a universal method, and fracture behaviors were characterized by scanning electron microscopy. According to the applied statistical approach results, the reliability of ceramic beds is controlled mainly by the binder type, humidity of paste, particle size distribution of fluxing agents and fillers. Between the studied factors, the roles of composition and humidity are predominant.
Is There a Global Safe Haven?
Authors: Habib Maurizio Michael , Stracca Livio
Published: December 2015

In this paper we search for global safe‐haven assets by analysing the impact of crisis episodes and risk shocks on the behaviour of foreign investors and selected asset prices and yields. We regress de‐trended net purchases by foreign investors of debt instruments issued in safe and liquid financial markets on estimated global risk‐aversion shocks and crisis episodes identified by both quantitative and qualitative means. On the price side, we also look at changes in long‐term government bond yields and the appreciation of the effective exchange rate conditional on risk shocks. We find that US short‐term debt – in particular government debt – is the best, though still imperfect, example of a global safe‐haven asset. In the majority of cases we find that foreign investors head for the exit.
Distances in multimedia phylogeny
Authors: Oikawa Marina A. , Dias Zanoni , Rocha Anderson , Goldenstein Siome
Published: December 2015

The distance between two objects determines how far apart they are with respect to each other. In this paper, we provide an overview of the distance concept in multimedia phylogeny, a novel research field that aims at discovering the phylogenetic relationships among digital objects that belong to the same population. With applications in digital forensics, copyright enforcement, and security, existing approaches are often based on dissimilarity computations among digital objects in a nonmetric space, but with enough information to correctly reconstruct the underlying relationships of these objects. As we discuss throughout the paper, a proper and well‐designed dissimilarity is paramount for differentiating whether two multimedia objects are related and, also, the directionality of such relationship. In phylogeny setups, there is also the additional requirement of low complexity: fast and accurate dissimilarity measures to cope with the massive amount of data we often have to handle.
Inhibition of cyclooxygenase‐1 and ‐2 activity in keratinocytes inhibits PGE2 formation and impairs vascular endothelial growth factor release and neovascularisation in skin wounds
Authors: Goren Itamar , Lee Seo‐Youn , Maucher Damian , Nüsing Rolf , Schlich Thomas , Pfeilschifter Josef , Frank Stefan
Published: December 2015

Inhibition of cyclooxygenase (Cox) enzymatic activity by non‐steroidal anti‐inflammatory drugs (NSAIDs) provides the molecular basis of analgesia following wounding or surgery. This study investigated the role of Cox activity in the regulation of vascular endothelial growth factor (VEGF) expression in keratinocytes and the formation of new blood vessels in acute wounds in mice. To this end, human HaCaT keratinocytes were stimulated with epidermal growth factor (EGF). EGF increased Cox‐1 mRNA in the presence of the constitutively expressed Cox‐1 protein in keratinocytes. EGF coinduced Cox‐2 and VEGF165 mRNA and protein expression and an accumulation of prostaglandin E2 (PGE2) in cell culture supernatants. Inhibition of Cox isozyme activity by Cox‐1 and ‐2 siRNA or ibuprofen reduced PGE2 and VEGF165 release from keratinocytes. In a mouse model of excisional wound healing, Cox‐2 and VEGF165 expression were colocalized in the granulation tissue of acute wounds. Oral treatment of mice with the Cox‐1 and ‐2 inhibitor diclofenac was associated with reduced levels of VEGF165 protein and an impaired blood vessel formation in acute wound tissue. In summary, our data suggest that a reduction of PGE2‐triggered VEGF165 protein expression in wound keratinocytes is likely to contribute to the observed impairment of wound neovascularisation upon Cox inhibition.
Antipyrine metabolite formation in children in the acute phase of malnutrition and after recovery.
Authors: Buchanan N , Davis M , Danhof M , Breimer DD
Published: December 2015

1. The plasma elimination rate of antipyrine and the urinary excretion of antipyrine and its primary metabolites 4‐hydroxy‐antipyrine, norantipyrine, 3‐hydroxymethyl‐antipyrine and 3‐carboxyantipyrine were measured in five children in the acute phase of malnutrition and after recovery. The results were compared with those obtained in 3 normal children. 2. Upon nutritional rehabilitation antipyrine clearance increased from 0.65 +/‐ 0.14 ml min‐1 kg‐1 to 1.07 +/‐ 0.20 ml min‐1 kg‐ 1. 3. The urinary excretion of 4‐hydroxy‐antipyrine increased from 6.1 +/‐ 4.5 to 14.7 +/‐ 5.9%, norantipyrine from 8.8 +/‐ 5.7 to 14.3 +/‐ 5.4 and 3‐hydroxy‐methyl‐antipyrine from 11.8 +/‐ 8.3 to 20.5 +/‐ 5.6% (% of dose/24h urine). Excretion of unchanged antipyrine decreased from 5.2 +/‐ 3.7 to 2.7 +/‐ 0.9% dose. The metabolite profile (ratio between the amounts of the various metabolites excreted) was not significantly different. 4. It is concluded that malnutrition decreases the rate of antipyrine metabolism, but it does not affect the three oxidative pathways differently.
A pharmacokinetic and tolerance study of Ro13‐9904, a new cephalosporin antibiotic.
Authors: Pickup ME , Bird HA , Lowe JR , Lees L , Wright V
Published: December 2015

1 Six healthy male volunteers received a total of 2500 mg of a new cephalosporin antibiotic Ro13‐9904 by intramuscular injection in five divided doses at intervals of 12 h. 2 No significant systemic side‐ effects were observed and this was confirmed haematologically and biochemically. 3 The drug was distributed following intramuscular injection reaching a mean peak plasma concentration of 55 micrograms ml‐ 1 (range 46‐66) 1 to 2 h after the first injection. 4 Monoexponential elimination of drug was demonstrated. No significant difference was recorded in the plasma half‐life after the initial dose (mean 6.7 h) and at steady state (mean 6.7 h). The half‐life is long compared with other cephalosporin antibiotics. 5 On the basis of the observed half‐ life, steady state should be reached within 48 h. A mean peak plasma concentration of 74 micrograms ml‐1 (range 65‐87) was recorded at steady state. Steady state plasma concentrations of Ro13‐9904 with a dose of 500 mg every 13 h may be predicted from the pharmacokinetics of a single dose.
Sublingual buprenorphine used postoperatively: clinical observations and preliminary pharmacokinetic analysis.
Authors: Bullingham RE , McQuay HJ , Dwyer D , Allen MC , Moore RA
Published: December 2015

1 Buprenorphine is a long‐acting opiate analgesic. This study was designed to investigate the pharmacokinetics of this drug when given by the sublingual route to ten postoperative patients. Plasma levels of buprenorphine were measured by a specific radioimmunoassay. 2 Plasma levels of the drug following sublingual administration of 0.4 mg showed an apparent delay in absorption and then rose slowly to reach low but significant levels by 3 h. There was considerable variation in the time at which peak levels were achieved. The average systemic availability of the drug by this route was estimated to be 30% by 3 h. 3 Analgesic efficacy and duration of sublingual buprenorphine were assessed using demand analgesia. The analgesia was of about 9 h duration, similar to that achieved by parenteral administration of 0.3 mg of the drug to an equivalent group of patients. The sublingual dose caused a significant fall in the postoperatively elevated group of patients. The sublingual dose caused a significant fall in the postoperatively elevated plasma glucose, and prevented any further rise in plasma cortisol. 4 Reasons for the efficacy of the sublingual route are discussed and it is suggested that this route may be particularly appropriate for highly lipophilic drugs like buprenorphine.
Some considerations on the role of benzodiazepines in the treatment of depression.
Authors: Cassano GB , Conti L
Published: December 2015

1 Benzodiazepines are regarded as pure anxiolytics, and their value in the treatment of depression is controversial. Nevertheless, symptoms of anxiety and depression coexist in patients with endogenous or neurotic depression, and clinical trials indicate that depressed patients respond better to a benzodiazepine‐tricyclic antidepressant combination than to either drug alone. 2 Benzodiazepines may extend tricyclic antidepression efficacy by rapidly relieving anxiety and insomnia. Factor analysis of scores obtained using the Hamilton Depression and Self‐Administered Depression Rating Scales confirm the clinical findings by revealing that a close correlation exists among anxiety, insomnia and endogenous depression. The factor analysis data seem to support the wide use of benzodiazepine‐tricyclic combinations to treat depressed patients.
The disposition and metabolism of sulphasalazine (salicylazosulphapyridine) in man.
Authors: Azadkhan AK , Truelove SC , Aronson JK
Published: December 2015

1 We have investigated the disposition and metabolism of sulphasalazine (SASP) in eight adults with and without inflammatory bowel disease. 2 SASP is poorly absorbed (less than 12%) and the half‐time measured in the serum, 10.2 h, is probably the half‐time of absorption and therefore an overestimate of the true half‐time. The apparent volume of distribution is low (less than 9 l). Renal and biliary clearance rates are low (5.5 and 2.1 ml min‐1 respectively) probably due to a high degree of protein binding. Of the absorbed SASP, two thirds is excreted in the urine and one third in the bile. 3 Most of the SASP reaches the colon and is there split by bacteria, forming sulphapyridine (SP) and 5‐ aminosalicylic acid (5‐ASA). 4 SP is almost completely absorbed and, with its metabolites, is excreted in the urine (SP renal clearance rate 32.1 ml min‐1). There is no enterohepatic recirculation. 5 Of the 5‐ASA released in the colon at least 25% is absorbed and rapidly eliminated in the urine after acetylation. At least 50% is eliminated in the faeces. 6 There are no differences in disposition characteristics when comparing patients with and without inflammatory bowel disease but the metabolism of SASP is markedly reduced in patients taking antibiotics and after removal of the large bowel.
Valproic acid and diazepam interaction in vivo.
Authors: Dhillon S , Richens A
Published: December 2015

1 The effect of oral administration of sodium valproate (1500 mg daily) on the distribution and elimination kinetics of intravenously administered diazepam in six healthy volunteers has been studied. 2 During valproate administration the unbound fraction of diazepam in serum increased approximately two fold. This was accompanied by a significant increase in apparent volume of distribution and plasma clearance of diazepam. 3 There was a positive correlation between the change in free fraction and the increase in both apparent volume of distribution and plasma clearance of the drug. 4 The concentration of unbound diazepam in serum (calculated from the percent free diazepam and total serum concentration) was significantly higher during valproate administration. Both the intrinsic clearance and volume of distribution of unbound drug were significantly reduced. 5 Mean serum N‐ desmethyldiazepam levels were significantly lower during valproate coadministration. 6 These results suggest that valproic acid displaces diazepam from plasma protein binding sites and inhibits its metabolism.
Aggregation and Species Discrimination in Newborn Snakes
Authors: Burghardt Gordon M.
Published: December 2015

In a study of the grouping tendencies of newborn snakes and their ability to discriminate each other by species, experiments were performed involving 20 brown snakes (Storeria dekayi) and 20 garter snakes (Thamnophis sirtalis) released in the same enclosure after being born on the same day. Both species were found most often under covers, and under some covers more than others. They were also more likely to be found in clumps involving conspecifics, but mixed aggregations were common and there was no evidence of repulsion. Species discrimination was demonstrated. Thamnophis aggregated more extensively than Storeria and Storeria was more spatially disoriented by disturbances to the environment.

Neugeborene Braunnattern (Storeria dekayi) und Strumpfbandnattern (Thamnophis sirtalis) wurden unmittelbar nach der Geburt in ein Terrarium mit Kiesboden und 8 Pappverstecken gegeben. Die 40 Schlangen (20 von jeder Art) wurden 11 Tage lang beobachtet. Nach fünftägiger allgemeiner Beobachtung (Verteilung der Schlangen auf deckungsbietende Objekte, Gruppenbildung mit Berührung) wurden folgende Manipulationen durchgeführt: Wechsel der deckungsbietenden Objekte, Käfigdrehung, Veränderung des Bodenbelags (Kies) sowie Entfernen der Schlangen aus dem Käfig für eine bestimmte Zeit.

Die Ergebnisse haben gezeigt: 1. Beide Arten haben die starke Neigung, sich unter Objekten zu verstecken; 2. Individuen beider Arten gesellten sich eindeutig zu artgleichen, besonders zu Gruppen; 3. Bestimmte Orte im Käfig waren anziehend für beide Arten; 4. Thamnophis war geselliger als Storeria, und 5. Gruppierungen von Storeria wurden durch Käfigmanipulationen stärker gestört.

Aggregationen und intraspezifisches Erkennen gibt es bei neugeborenen Schlangen; es ist von Art zu Art unterschiedlich und wird wahrscheinlich durch das Vomeronasalorgan vermittelt.
Antipredator Benefits of Schooling Behaviour in a Cyprinodontid Fish, the Banded Killifish (Fundulus diaphanus)
Authors: Morgan M. Joanne , Godin Jean‐Guy J.
Published: December 2015

Fish schools are believed to provide antipredator benefits to their members. Two potential antipredator benefits, the dilution and confusion effects, of schooling were investigated in the laboratory using banded killifish (Fundulus diaphanus). Individual risk of being attacked and killed by a fish predator (white perch, Morone americana) declined with increasing killifish school size in a manner closely predicted by the dilution hypothesis. Perch were apparently not confused by schooling killifish since fish in groups of one did not suffer a disproportionately greater predation rate than fish in all larger school sizes. However, killifish straggling from the school were preferentially attacked and more successfully captured compared with school members. Schooling in the banded killifish therefore confers a considerable antipredator benefit to individual group members, at least through a dilution effect, and straying from a school has an associated increased risk of mortality to predation, which selects for schooling behaviour.
Selective inhibition of inducible cyclo‐oxygenase‐2 expression by antisense peptide nucleic acids in intact murine macrophages
Authors: Scarfì Sonia , Giovine Marco , Pintus Raffaela , Millo Enrico , Clavarino Emanuela , Pozzolini Marina , Sturla Laura , Stock Roberto Pablo , Benatti Umberto , Damonte Gianluca
Published: December 2015

Prostaglandins are important molecules involved in inflammation and immunomodulation. The rate‐limiting step in the synthesis of these potent mediators is the expression of the enzyme cyclo‐oxygenase (COX). The isoform responsible, COX‐2, is encoded by an immediate‐early gene induced by various pro‐inflammatory agents in macrophages. Selective blockade of COX‐2 by the use of an antisense strategy would overcome the undesirable side effects of conventional inhibitors. Here we describe cellular internalization and activity of a novel class of oligonucleotide analogues named peptide nucleic acids (PNAs) as inhibitors of COX‐2 translation. In particular, we designed two antisense murine COX‐2 PNA molecules, directed against a mRNA region spanning the AUG translation‐initiation codon and a homopurinic sequence inside the COX‐2 mRNA reading frame. These two PNA sequences, used separately or mixed together, demonstrated the capacity to inhibit the translation of murine COX‐2 enzyme in a cell‐free translation model using a rabbit retculocyte lysate model. Since PNAs display very low natural permeability across lipids bilayers, the two molecules were also re‐synthesized, modified to be used in intact cells by means of linkage to a hydrophobic peptide to obtain membrane‐diffusable PNA chimaerae. Finally, stimulated macrophages were found to be affected strongly by these two compounds, used separately or together, monitoring inhibition of COX‐2 synthesis by Western blot analysis of total lysates and enzymic activity via radioactive assay on the microsomal fractions.
Maternal Antibodies to Paternal B‐Lymphocytes in Normal and Abnormal Pregnancy
Authors: POWER D.A. , MATHER A.J. , MACLEOD A.M. , LIND T. , CATTO G.R.D.
Published: December 2015

ABSTRACT: Sera were obtained prior to conception and during the first trimester of subsequent pregnancies from 22 women over 27 pregnancies; on 15 occasions these pregnancies ended in spontaneous abortion, whereas the remaining 12 achieved live normal babies. In only one pregnancy ending in abortion could antibodies directed to paternal B‐lymphocytes determined by the EA rosette inhibition (EAI) assay be detected in the mother's serum, whereas five of the 12 successful pregnancies were associated with such detectable antibodies. Cytotoxic antibodies were also found in all but one of these EAI‐positive pregnancies and no antibody activity was present in sera obtained from five primigravidae. These results indicated that normal, but not abnormal, pregnancies were often associated with blocking antibody formation, suggesting that such antibodies may protect the fetus from abortion. However, the failure to detect antibody activity in sera from first trimester primigravidae argues against a central role for blocking antibody, alone, in the maintenance of outbred pregnancy.
Thymus‐Dependent Increase in Splenic T Cell Population in Postpartum Mice
Authors: YOKOYAMA MOTOFUMI , KOGA YASUHIRO , TANIGUCHI KAZUTO , NAKANO HITOO , NOMOTO KIKUO
Published: December 2015

ABSTRACT: Cell dynamics in the thymus and spleen of mice during the first allogeneic pregnancy and during postpartum were investigated. A considerable decrease in the number of thymocytes occurred at midpregnancy and was sustained until postpartum. There was an increase in the number of splenic T cells on the third postpartum day. These splenic T cells were shown to have the Lyt‐1+ 2− phenotype, as determined by multiparameter analysis, and their responsiveness to Con A was increased compared with splenic T cells of virgin mice. Since such T cells were not observed in the postpartum spleen of adult thymectomized mice, they may have derived from the thymus. The response to Con A by normal virgin spleen cells was depressed when spleen cells from 3‐day postpartum mice were added to the culture as the third party cells. Thus, the increased number of splenic T cells may act as inducer cells in the suppressor circuit during postpartum.
Further Characterization of a Human Sperm Coating Antigen (gp12)
Authors: SAJI FUMITAKA , MINAGAWA YOSHIO , OHASHI KAZUTOMO , NEGORO TAKAO , TANIZAWA OSAMU
Published: December 2015

ABSTRACT: In our previous paper, we identified a novel sperm‐coating antigen with molecular weight of approximately 12,000 daltons that is highly specific to sperm, seminal plasma, and milk from the plasma membrane fraction of human spermatozoa by using rabbit antiseminal plasma antiserum. In the present study, this 12,000‐daltons component, termed gp12, has been investigated for its tissue distribution and antigenic stability. The largest amounts of the antigen are found in seminal plasma, although individual variation is rather high. In seminal plasma, the gp12 molecule presents in a large form with a molecular weight of approximately 50,000 daltons. Its antigenicity is stable when treated with acid, alkali, heat, and various protein denaturants.
Maternal and Fetal Circulating Levels of Thymosin α1 During Parturition
Authors: WELCH ROBERT A. , MUTCHNICK MILTON G. , WELLER FREDERICK E. , SOKOL ROBERT J.
Published: December 2015

ABSTRACT: The thymus directs T‐lymphocyte development and contributes to the maintenance of immune homeostasis, in part, through its production of peptides known as thymosins. In pregnancy, maternal serum levels of thymosin α1 have been reported to be low at midgestation and to increase by term, suggesting that maternal levels represent fetal levels. To evaluate this further, we obtained maternal venous and newborn mixed cord blood from 90 pregnancies between 20 and 42 weeks of gestation at delivery. An ELISA was used for thymosin α assay, and analysis was by paired t test and regression. Maternal and newborn levels were independent of gestational age, but an apparent association (r = 0.51) between the two was inconclusive. Maternal levels (1,207 ± 947 pg/ml) tended to be higher than those of healthy adults (1,043 ± 576 pg/ml). Mixed umbilical cord serum levels (1,466 ± 940 pg/ml) were higher than maternal levels (P ≤ 0.005). Although maternal thymosin α levels may reflect fetal levels, immunological perturbations related to parturition appear to influence both.
Trophoblast Does Not Cause the Cytotoxic T Lymphocyte Generation Due to the Lack of Ability to Stimulate lnterleukin‐2 Production
Authors: BLANK M. , NEBEL L. , TODER V.
Published: December 2015

ABSTRACT: Trophoblast was demonstrated to be unable to cause the production of interleukin‐2 (IL‐2) by allogeneic splenocytes in vitro in two ways: 1) The addition of lymphocyte‐trophoblast culture‐supernatant (LTC‐SN) did not stimulate the proliferation of IL‐2 dependent cytotoxic T lymphocyte (CTL‐L cells; 2) When responder cells were cultured with heat‐treated splenocytes (usually no CTL generation) an increase of CTL formation could be seen in the presence of mixed lymphocyte culture‐supernatant (MLC‐SN) but not of SN from the cultures in which trophoblast cells served as stimulators. In parallel, the trophoblast cells were found to be very poor stimulators of alloreactive CTL. The addition of interleukin‐2‐enriched media resulted in a significant amplification of trophoblast‐induced CTL generation. The resulting killing lymphocytes were capable of destroying the only specific targets, did not lyse syngeneic target cells, and could not be generated in the absence of allogeneic trophoblast. The incubation of these lymphocytes with anti‐Thy 1.2 monoclonal antibody in the presence of complement eliminated their killing effect. Lack of class II antigenic determinants on the surface of trophoblast and/or local immunosuppression of IL‐2 production by trophoblast cells seem to be responsible for nondelivery of helper factor, which is essential for CTL production.
Indirect Mixed Antiglobulin Reaction (MAR) as a Screening Procedure for Antisperm Antibodies. I. Methodological Studies
Authors: MEINERTZ HELLE
Published: December 2015

ABSTRACT: Direct mixed antiglobulin reaction (MAR) cannot always be carried out because it requires motile spermatozoa in the patient's ejaculate. Therefore, the indirect MAR for IgG and IgA using donor spermatozoa sensitized with serum or seminal plasma from patients was investigated with the aim of developing a practical screening procedure for antisperm antibodies involving a characterization of the Ig‐class of the antibodies.

Samples from 23 men, 13 men with and 10 men without agglutinating antisperm antibodies, were used for the methodological experiments with the indirect MAR. Among three procedures to diminish the amount of nonbound immunoglobulin after sensitizing the donor spermatozoa with serial dilutions of serum or seminal plasma, a swim‐up method was found to be optimal. The indirect MAR was carried out with glutaraldehyde‐fixed sheep erythrocytes coated with IgG or IgA and various dilutions of anti‐IgG and anti‐IgA, respectively.

These experiments led to a standardization of the indirect MAR, making it sensitive, easy to read, and allowing the reactions for IgG and IgA to be compared on an approximately equimolecular basis.
Study on Nonspecific Immunity in Pregnant Women: Increased Chemiluminescence Response of Peripheral Blood Phagocytes
Authors: SHIBUYA TAKAHIRO , IZUCHI KUNIO , KUROIWA ATARU , OKABE NOBUO , SHIRAKAWA KOICHI
Published: December 2015

ABSTRACT: The total number of circulating leucocytes in the peripheral blood of pregnant women progressively increased with advance in gestation because of neutrophilia. When the phagocytic activity, representing nonspecific immunity, was estimated by a luminol‐dependent chemiluminescence (CL) response during phagocytosing opsonized zymosan, we observed that the CL response of whole blood and Ficoll‐Paque separated polymorphonuclear leucocytes (PMNL) significantly increased throughout the pregnancy (P<0.01). The CL responses of mononuclear leucocytes (MN) and monocytes also increased and reached peak levels in the third trimester (P<0.05). These findings suggest that the phagocytic activity in pregnant women increases, not only with regard to the number of phagocytes but also with regard to individual cell function, from a relatively early stage of the pregnancy, and that this increased nonspecific immunity may compensate in part for a weakened specific immunity of the maternal host. Attention should be directed to effects of human chorionic gonadotropin (hCG) relative to the increased CL response during pregnancy.
Immunology of Recurrent Vaginitis
Authors: WITKIN STEVEN S.
Published: December 2015

ABSTRACT: Recent evidence suggests that recurrent vaginitis can arise as a consequence of a transient and localized inhibition of cell‐mediated immunity. Lymphocytes from many women with this disorder manifest a reduced in vitro proliferative response to Candida albicans. The inhibition appears to be due to increased production by the patients' macrophages of prostaglandin E2, which inhibits interleukin‐2 production and thereby blocks lymphocyte proliferation. When lymphocyte responses are impaired, C. albicans can readily proliferate and initiate a clinical infection. Prostaglandin E2 production can arise as a consequence of a vaginal allergic response. IgE antibodies to C. albicans, ryegrass, contraceptive spermicides, and seminal plasma have been detected in vaginal fluids from recurrent vaginitis patients. The role of male factors in inducing immune alterations and vaginitis in the female partner has been underestimated. Medications or chemicals ingested by the male and present in his semen may be transmitted to sensitized females by coitus. In addition, male‐specific allergic responses may be induced in females through the seminal transfer of specific IgE antibodies, future efforts both to eliminate clinical vaginal infections and to reduce susceptibility of the host to vaginal immunosuppression should improve the efficacy of treatment for this disorder.
Death‐Related Attitudes and Behavior among Mexican Americans: A Review
Authors: Markides Kyriakos S.
Published: December 2015

ABSTRACT: A review of the literature on death‐related attitudes and behavior of Mexican Americans is presented. Special focus is given to the 1976 study of Kalish and Reynolds which concludes that Mexican Americans are more accepting of death than Anglos and other ethnic groups. Some of the study's findings are found to suggest that the opposite may be true. An alternative interpretation of the findings is given along with suggestions for future research.
Adolescent Suicide Attempts: Some Significant Factors
Authors: Tishler Carl L. , McKenry Patrick C. , Morgan Karen Christman
Published: December 2015

ABSTRACT: A group of 108 adolescents who attempted suicide over a two‐year period is described. Significant factors related to these attempts are presented and discussed. These adolescent suicide attempts are most significantly related to long‐term family dysfunction. Some vegetative depressive symptoms are noted in a majority of patients. Implications are drawn for strengthening the mental health practitioner's role in detecting and preventing adolescent suicide.
Indirect Self‐Destructive Behavior in Chronic Hemodialysis Patients
Authors: Gerber Kenneth E. , Nehemkis Alexis M. , Farberow Norman L. , Williams John
Published: December 2015

ABSTRACT: As one of a series of investigations of indirect self‐destructive behavior, a pilot study was conducted with a group of 32 chronic hemodialysis patients for those characteristics of such behavior which had emerged as most salient in earlier studies: self‐esteem, locus of control, rigidity, impulsivity, futurity, risk‐taking and denial. Using an average of ratings of cooperativeness obtained from the head nurse, physician, dietician, technician, and staff nurse, the group was divided into two subgroups of more and less cooperative patients, and the demographic, medical, and psychological data from the two groups were compared. The findings suggest that the less cooperative hemodialysis patients have experienced the illness as a more severe blow to their self‐concept and have failed to integrate their illness into an effective adaptive life pattern. The uncooperative patients feel less valued and less appreciated not only by their family but also by fellow patients and by hospital staff. They show significantly more anger and withdrawal than the more cooperative group and appear to have compensated for a significantly greater sense of powerlessness by the development of manipulative behaviors in relating to their medical caretakers.
Suicide: Bad Act or Good Intervention
Authors: Clements Collen D. , Sider Roger C. , Perlmutter Richard
Published: December 2015

This article develops a different perspective on the ethics of suicide, based on theoretical and clinical grounds. In terms of value theory, applying “good” or “bad” to the suicide act makes no sense. We need to shift our focus from a search for an ethical statement about suicide (e.g., “rational suicide”) to the ethical justification for intervention based on the needs and interests of an affirming therapeutic profession. We choose to intervene because of values we hold about well‐functioning, existence, potential for human life; and because as empathic, social beings, we feel for others and are motivated by that feeling. This justification leads us to suggest a situational case‐centered ethics for suicide intervention.
Proposal for a Distinctive Diagnosis: the Deliberate Self‐Harm Syndrome (DSH)
Authors: Kahan Joel , Pattison E. Mansell
Published: December 2015

ABSTRACT:Self‐destructive behavior is a major clinical problem in psychiatry. A review of the literature reveals the existence of enough clinical data to identify a diagnostic entity, “The Deliberate Self‐Harm Syndrome” (DSH). The authors present a diagnostic formulation of the DSH syndrome (in the DSM‐III format) which consists of four essential clinical features, a group bof associteds features, clinical features, a group of associated features, a clinical course of typical onset in late adolescence, with multiple recurent episodes, with multiple methods of low lethality physical self‐injury, extending over many years. On the basis of relatively exclusive association of clinical signs and symptoms a heuristic clinical entity is proposed.
A Reciprocal Control Approach to the Treatment of Repeated Parasuicide
Authors: Zich Jane M.
Published: December 2015

ABSTRACT: Patterson and Reid's formulation of coercive versus reciprocal control offers a theoretical model for understanding both parasuicide and nontherapeutic exchanges between treatment staff and repeat suicide attempters. An interpersonal treatment program, derived from the Patterson and Reid formulation, which has been consistently associated with positive changes in the course of hospitalization for moderate‐risk inpatients, is outlined, followed by a case illustration and discussion of the treatment strategy. The article stresses the importance of targeting the interpersonal environment as well as parasuicidal acts in the treatment program for repeat suicide attempters.
Environmental and Personality Similarities in Case Histories of Suicide and Self‐Poisoning by Children Under Ten
Authors: Corder Billie F. , Haizlip Thomas M.
Published: December 2015

ABSTRACT: Research on suicide in latency age children is reviewed and case histories of two 9‐year‐old children who suicided by shooting themselves and one 7‐year‐old who died by self‐poisoning are presented. Similarities in environmental and family histories, and in personality variables among these three cases have suggested underlying mechanisms in development and maintenance of symbiotically shared self‐concept between parent and child which may be useful in helping to identify similar cases and in assessing potential for suicidal and self‐destructive behavior in latency age children.
A Critical Look at Our Adolescence: Notes on Turning 18 (and 75)
Authors: Berman Alan L.
Published: December 2015

ABSTRACT: Within the contexts of both the American Association of Suicidology's (AAS's) history and the history of associating suicidologists, an integrative identity based on the tenets of science is urged for the AAS. Two propositions are made: first, that we must promote and adopt more discriminative, standardized terminology; second, that we must promote and implement standards of informational competency for professionals and paraprofessionals alike.
Social Life Factors Affecting Suicide in Japanese Men and Women
Authors: Araki Shunichi , Murata Katsuyuki
Published: December 2015

ABSTRACT: To clarify the social life factors affecting suicide mortality in Japanese men and women, the relationship between a wide variety of social and demographic indicators and age‐adjusted suicide mortality was assessed in 46 prefectures in Japan by stepwise multiple‐regression analysis after classification of the indicators by factor analysis. The findings indicated that rural residence was the major factor for male mortality in both 1970 and 1975; over the interval between these years, a serious economic crisis (the oil crisis) took place, and the mortality significantly increased. In addition, in 1970 (a time of high economic growth), home help for the elderly (a possible indicator of social isolation in old people), depopulation by social mobility, and urban residence were positively associated with male mortality. In women, on the other hand, both the 5‐year increase in suicide mortality and the effects of the social life factors were less significant. The unique position of Japan in comparison with Western countries regarding social risk factors for suicide is discussed in the light of these findings.
The Prevalence of Suicidal Ideation among College Students
Authors: Rudd M. David
Published: December 2015

ABSTRACT: A total of 737 university students were surveyed using a psychometrically sound self‐report measure of suicidal ideation. Over 43% of those participating were found to have experienced some level of suicidal ideation during the previous year. Of those found to have had suicidal thoughts, 14.9% in some way acted on those thoughts without actually making suicide attempts. An additional 5.5% were found to have made attempts on their lives. Serious suicidal ideation and actual attempts were related to several demographic traits, and implications of the results are discussed. In general, findings indicate that the problem of youth suicide may involve a greater percentage of young people than previously thought. Moreover, findings provide indirect support for the hypothesis that the difference in male‐female completed suicide rates is primarily a function of the lethality of the attempts.
In situ marker‐based assessment of leaf trait evolutionary potential in a marginal European beech population
Authors: Bontemps A. , Lefèvre F. , Davi H. , Oddou‐Muratorio S.
Published: December 2015

Evolutionary processes are expected to be crucial for the adaptation of natural populations to environmental changes. In particular, the capacity of rear edge populations to evolve in response to the species limiting conditions remains a major issue that requires to address their evolutionary potential. In situ quantitative genetic studies based on molecular markers offer the possibility to estimate evolutionary potentials manipulating neither the environment nor the individuals on which phenotypes are measured. The goal of this study was to estimate heritability and genetic correlations of a suite of leaf functional traits involved in climate adaptation for a natural population of the tree Fagus sylvatica, growing at the rear edge of the species range. Using two marker‐based quantitative genetics approaches, we obtained consistent and significant estimates of heritability for leaf phenological (phenology of leaf flush), morphological (mass, area, ratio mass/area) and physiological (δ13C, nitrogen content) traits. Moreover, we found only one significant positive genetic correlation between leaf area and leaf mass, which likely reflected mechanical constraints. We conclude first that the studied population has considerable genetic diversity for important ecophysiological traits regarding drought adaptation and, second, that genetic correlations are not likely to impose strong genetic constraints to future population evolution. Our results bring important insights into the question of the capacity of rear edge populations to evolve.