Plasma prolactin concentrations in parental male and female rats: effects of exposure to rat young

The effects of pup presentation on the PRL responses in parental male rats were measured and compared with those in parental virgin and lactating female rats. Blood samples were collected from rats through indwelling intraatrial cannulas after a suckling challenge, i.e. presentation of rat young. Lactating rats showed full parental behavior and characteristic large surges in plasma PRL levels within the first 5-10 min on each day that rat young were presented (days 4, 8, and 12 of lactation). When pups were not presented, PRL rises did not occur. In contrast to the pattern of PRL responses shown by lactating mothers, parental ovariectomized nulliparous female and parental intact male rats failed to show specific increases in PRL in response to pup presentation. Plasma PRL levels in these groups, as in nonparental female and male rats, occasionally rose in response to blood collection rather than to pup presentation alone. Treatment of nulliparous female as well as male rats with estradiol and progesterone Silastic implants for 21 days before the initiation of behavioral testing significantly reduced the latencies of both nulliparous females and males to respond to foster young from about 5 to 2 days. The PRL responses of these steroid-primed groups were quite different. The steroid-primed females exhibited a pattern of PRL responses to pups identical to that found in lactating rats. The steroid-primed parental males, in contrast, failed to show specific increases in plasma PRL levels in response to young. These data demonstrate a sex difference in the hormonal, but not behavioral, responses of male and female rats to young and are suggestive of possible sex differences in the hypothalamic and/or peripheral regulation of pup-induced PRL secretion.     

Opioid receptor subtype involvement in maternal behavior in lactating rats.

Central or systemic administration of morphine disrupts maternal behavior in steroid-primed, pup-induced virgin and lactating rats. Morphine, the prototypical mu agonist, also interacts with different opioid receptor subtypes. The present study examined the effectiveness of five receptor-selective agonists, in addition to morphine, to disrupt maternal behavior in primiparous lactating rats following intracerebroventricular (i.c.v.) infusions in order to characterize opioid receptor subtype involvement in maternal behavior in the female rat. Virgin, Sprague-Dawley rats were mated and implanted with lateral ventricle cannulae on days 13-15 of gestation. On postpartum day 5, mothers were tested for maternal behavior 30 min after i.c.v. vehicle infusion (5 microliters). On day 6, rats received one of the following opioid receptor agonists 30 min before testing: beta-endorphin (mu/epsilon receptor subtype; 0.29, 0.72, 1.45, 2.9 nmol), DAGO (mu; 0.29, 0.72, 1.45, 2.9 nmol), morphine (mu; 0.29, 0.72, 1.45, 2.9, 14.5 nmol), DPDPE (delta; 2.9, 29 nmol), U50488H (kappa l; 2.9, 29, 145 nmol) and SKF10047 (sigma; 2.9, 29, 145 nmol). Only activation of mu opioid receptors dose-dependently disrupted maternal behavior in primiparous lactating rats. DPDPE, U50488 and SKF10047 had no discernible effect on maternal behavior. DAGO, a highly selective mu agonist, was even more potent than beta-endorphin and morphine in disrupting maternal behavior suggesting that maternal behavior is regulated by opioids interacting with the mu opioid receptor.     

Influence of High and Low Autonomy-Supportive Climates on Physical Activity in Children with and without Developmental Disability

The aim of this study was to compare the influence of two different instructional climates on the accumulation of moderate-to-vigorous physical activity (MVPA) during a fully-inclusive adapted recreational physical activity program. A total of 32 children (18 typically-developing (TD), and 14 with developmental disabilities (DD) ranging in ages from 5 to 9 years, participated in six, 60-min adapted recreational sessions. Of those six sessions, three incorporated an autonomy-supportive climate (high autonomy), and three incorporated direct instruction (low autonomy). MVPA was measured using accelerometers. A repeated measures ANOVA was conducted to determine significant differences in MVPA between group (TD/DD), climate (autonomy/direct), and a group x climate interaction. Significant group and climate main effects were observed (p?=?0.002 and 0.014, respectively). However, there was not a significant group x climate interaction (p?=?0.313). These results suggest that although the group of children with disabilities spent less time in MVPA compared to their typically-developing peers, all participants spent more time in MVPA for the autonomy-supportive climate compared to the low-autonomous climate. This study is the first to quantitatively assess the efficacy of a fully-inclusive autonomy-supportive climate on physical activity levels in children with and without developmental disabilities.     

Suckling and LH-induced progesterone secretion in lactating hamsters (Mesocricetus auratus).

The effects of suckling and LH upon serum progesterone levels in lactating hamsters were investigated. Diurnal rhythms in serum levels of progesterone and LH occur throughout lactation in the hamster and these levels are normally higher between 15.00 and 17.00 than between 8.00 and 12.00 (lights on 6.00-20.00). Hamsters injected with 10 mug of LH at 8.00 on day 9 of lactation had higher levels of serum progesterone 2 h after injections than did vehicle-injected controls. Suckling was also found to induce an increase in serum progesterone concentrations. 30 min of suckling from 10.30 to 11.00 on days 10 or 11 of lactation resulted in increased serum levels of progesterone and prolactin, but had no measurable effect upon serum LH levels in animals bled at 11.00. However, suckling for 30 min from 15.00 to 15.30 had no effect upon serum progesterone levels, although it did result in increased titers of both serum LH and prolactin at 15.30. Ovariectomy on day 7 of lactation resulted in lowered levels of serum progesterone at 11.00 on day 11 of lactation and abolished the suckling-induced increase in serum progesterone concentrations. These findings suggest that in the lactating hamster (1) suckling bouts stimulate progesterone secretion from the ovaries, and (2) the diurnal rise in serum progesterone levels is stimulated in part by the increase in serum levels of LH.     

Prolactin (PRL) regulation of maternal behavior in rats: bromocriptine treatment delays and PRL promotes the rapid onset of behavior

Recent findings indicate that PRL helps stimulate the onset of maternal behavior in inexperienced hypophysectomized steroid-treated female rats. In a series of five experiments we have further examined the involvement of PRL in maternal behavior using nonhypophysectomized ovariectomized rats treated concurrently (type I) or sequentially (type II) with progesterone (P) and estradiol (E2) and administered either bromocriptine (to suppress endogenous PRL secretion) or bromocriptine plus ovine PRL. In Exp 1 plasma PRL concentrations were measured in ovariectomized rats treated for 2 weeks with a combination of E2 and P Silastic implants. Type I steroid-treated (2mm E2, days 1-24; three 30 mm P, days 3-13) rats exhibited elevated plasma PRL levels throughout the sampling period compared with nonsteroid-treated controls. In contrast, PRL concentrations in type II steroid-treated (P, days 3-13; E2, days 13-24) females were low (similar to controls) from days 3-13 when the type II steroid-treated females were exposed to P only. Like type I treated rats, PRL levels in type II steroid-treated rats were elevated from day 13 onward after E2 capsule insertion. In Exp 2, treatment of both type I and type II steroid-treated rats with bromocriptine (2 mg/kg, sc) twice daily beginning on treatment day 13 suppressed basal PRL concentrations and prevented the estrogen-induced diurnal PRL surge. Whereas PRL was effectively suppressed by bromocriptine in both steroid-treated groups, the absolute levels of PRL were lower in rats treated with the type II steroid regimen. Behavioral analyses in Exp 3, 4, and 5 revealed that bromocriptine administration, while failing to interfere with the onset of maternal behavior in rats treated with the type I concurrent steroid regimen, disrupted the onset of maternal care in rats treated with the type II sequential steroid regimen. When a separate set of type II steroid-treated rats was given both bromocriptine (2 mg/kg) plus ovine PRL (0.5 mg, sc) twice daily, maternal behavior rapidly appeared. Thus, suppression of endogenous PRL secretion delays the onset of maternal behavior in nonhypophysectomized steroid-primed rats, an effect prevented by concurrent administration of ovine PRL. In addition to providing further experimental support for PRL's role in maternal behavior, the development of this endocrine regimen provides researchers with a potentially fruitful model to examine neural sites and mechanisms of PRL regulation of maternal behavior in mammals.     

G6PD San Francisco: a new variant of glucose-6-phosphate dehydrogenase associated with congenital nonspherocytic hemolytic anemia

Congenital nonspherocytic hemolytic anemia in an adult male of Scandinavian ancestry was associated with virtual absence of G6PD activity in red cells. Characterization of G6PD purified from leukocytes using standard WHO techniques revealed diminished electrophoretic mobility, marked lability on heating at 46 degrees C, normal pH optimum and utilization of alternate substrates (2-deoxy G6P, D-amino NADP), elevated Km NADP, and striking susceptibility to NADPH inhibition. The variant G6PD, which appears to be unique, has been designated G6PD San Francisco. An unusual feature of the variant enzyme, susceptibility to inactivation by brief periods of dialysis, could be prevented by addition of 200 microM NADP to the dialysis solution. In red cells, where G6PD activity was essentially absent, regeneration of reduced glutathione was totally curtailed in vitro, while in leukocytes, where residual G6PD activity was approximately 60% of normal, hexose monophosphate shunt activity, oxygen consumption during phagocytosis, and bacterial killing were unimpaired. Thus, instability of the variant enzyme rather than its unfavorable kinetics appeared to be an important determinant of abnormal cell function.     

Orthodeoxia-platypnea due to intracardiac shunting relief with transcatheter double umbrella closure

The safety and efficacy of transcatheter clamshell occlusion of patent foramen ovale for relief of severe arterial desaturation and dyspnea in the upright position due to intracardiac shunting were examined in eight patients with excessive risk of surgical patent foramen ovale closure. All patients had successful reduction of intracardiac shunting with an immediate rise in oxygen saturation ?95% by implantation of a clamshell device on the atrial septum. Despite two early incidents of device embolization, retrieval and immediate re-implantation, and one patient with nonsustained atrial and ventricular arrhythmias, there were no adverse clinical sequelae. In follow-up evaluation transcatheter clamshell closure of patent foramen ovale has provided persistent relief from shuntrelated arterial desaturation and symptomatology in all living patients. © 1995 Wiley-Liss, Inc.     

Transforming growth factor-beta 1 cooperates with anti-immunoglobulin for the induction of apoptosis in group I (biopsy-like) Burkitt lymphoma cell lines

Group I Burkitt lymphoma (BL) cell lines, which retain the original biopsy phenotype, have been shown to enter apoptosis in response to a number of external stimuli including serum deprivation, thermal shock, addition of calcium ionophore, and ligation of surface immunoglobulin (Ig) by antibody. Transforming growth factor-beta 1 (TGF beta 1) is known to cause growth arrest in BL lines. Here we show that while it is by itself capable of promoting some degree of apoptosis in group IBL cells, TGF beta 1 cooperates with anti-immunoglobulin to this end. Trimeric soluble recombinant human CD40 ligand (sCD40L) was able to inhibit apoptosis induced by the combination of agonists to some degree, but such rescue proved to be short-lived. Both TGF beta 1 and anti-Ig individually caused BL cells to undergo growth arrest at the G1 phase of cell cycle before their entry into apoptosis: the consequence of sCD40L addition was to maintain the cells in cycle for longer. No induction of the apoptosis-protecting gene, bcl-2, occurred in the presence of sCD40L. These findings are discussed, particularly highlighting the relationship existing between survival and the cell cycle. The strong cooperative effects observed between anti-Ig and TGF beta 1 in promoting apoptosis and the inability of CD40 to signal for long-term rescue raise the potential for a novel therapeutic attack on B-cell lymphoma.     

Moderation of hemophilia A phenotype by the factor V R506Q mutation

Although many examples of unrelated hemophilia A patients carrying identical point mutations in the factor VIII (FVIII) gene have been reported, the clinical phenotype is not always the same among patients sharing the same molecular defect. Possible explanations for this discrepancy include undetected additional mutations in the FVIII gene or coinheritance of mutations at other genetic loci that modulate FVIII function. We report molecular genetic analysis of potential modifying genes in two sets of unrelated patients carrying common FVIII missense mutations but exhibiting different levels of clinical severity. Both mutations (FVIII R1689C and R2209Q) are associated with severe hemophilia A in some patients and mild/moderate disease in others. The common von Willebrand disease type 2N mutation (R91Q) was excluded as a modifying factor in these groups of patients. However, analysis of the recently described factor V (FV) R506Q mutation (leading to activated protein C resistance) identified a correlation of inheritance of this defect with reduced hemophilia A severity. Two moderately affected hemophilia A patients, each with either of two FVIII gene mutations, were heterozygous for FV R506Q, whereas two severely affected patients and two moderately affected patients were homozygous normal at the FV locus. Our results suggest that coinheritance of the FV R506Q mutation may be an important determinant of clinical phenotype in hemophilia A and that modification of the protein C pathway may offer a new strategy for the treatment of FVIII deficiency.     

Interferon Gamma ELISPOT Testing as a Risk‐Stratifying Biomarker for Kidney Transplant Injury: Results From the CTOT‐01 Multicenter Study

Previous studies suggest that quantifying donor‐reactive memory T cells prior to kidney transplantation by interferon gamma enzyme‐linked immunosorbent spot assay (IFNγELISPOT) can assist in assessing risk of posttransplant allograft injury. Herein, we report an analysis of IFNγELISPOT results from the multicenter, Clinical Trials in Organ Transplantation‐01 observational study of primary kidney transplant recipients treated with heterogeneous immunosuppression. Within the subset of 176 subjects with available IFNγELISPOT results, pretransplant IFNγELISPOT positivity surprisingly did not correlate with either the incidence of acute rejection (AR) or estimated glomerular filtration rate (eGFR) at 6‐ or 12‐month. These unanticipated results prompted us to examine potential effect modifiers, including the use of T cell‐depleting, rabbit anti‐thymocyte globulin (ATG). Within the no‐ATG subset, IFNγELISPOT^neg subjects had higher 6‐ and 12‐month eGFRs than IFNγELISPOT^pos subjects, independent of biopsy‐proven AR, peak PRA, human leukocyte antigen mismatches, African‐American race, donor source, and recipient age or gender. In contrast, IFNγELISPOT status did not correlate with posttransplant eGFR in subjects given ATG. Our data confirm an association between pretransplant IFNγELISPOT positivity and lower posttransplant eGFR, but only in patients who do not receive ATG induction. Controlled studies are needed to test the hypothesis that ATG induction is preferentially beneficial to transplant candidates with high frequencies of donor‐reactive memory T cells.