Growth hormone binding protein in normal and aneuploid pregnancy: a paradoxical decrease in trisomy 18

Objective To explore whether abnormalities in growth hormone binding protein (GHBP) may underlie the growth restriction associated with fetal aneuploidy. Design A retrospective casecontrol study. Setting Monash Medical Centre, Clayton, Victoria, Australia. Population Twenty-one trisomy 18, and 30 trisomy 21 pregnancies, and 170 chromosomally normal pregnancies at 15-18 weeks of gestation representing three to five controls per case matched for source, gestation and duration of storage. Methods GHBP was measured using a ligand immunofunctional assay. Results In the chromosomally normal pregnancies GHBP levels decreased slightly but significantly across the narrow gestational window studied. Compared with controls, levels of GHBP, expressed as median (95% CI) multiples of the median (MoM), in the trisomy 21 pregnancies were similar, 1.0 (0.92-1.39) MoM and 1.27 (1.04-1.50) MoM, respectively; P = 0.061 (Mann-Whitney CI test) but were significantly reduced in the trisomy 18 pregnancies, 0.68 (0.51-0.84) MoM; P = 0.0014 (Mann-Whitney U test). Conclusions These data suggest that decreased levels of maternal growth hormone binding protein, and by implication growth hormone receptor complement, may underlie the early severe growth restriction that is characteristic of trisomy 18.

Causal and localizable quantum operations

We examine constraints on quantum operations imposed by relativistic causality. A bipartite superoperator is said to be localizable if it can be implemented by two parties (Alice and Bob) who share entanglement but do not communicate, it is causal if the superoperator does not convey information from Alice to Bob or from Bob to Alice. We characterize the general structure of causal complete-measurement superoperators, and exhibit examples that are causal but not localizable. We construct another class of causal bipartite superoperators that are not localizable by invoking bounds on the strength of correlations among the parts of a quantum system. A bipartite superoperator is said to be semilocalizable if it can be implemented with one-way quantum communication from Alice to Bob, and it is semicausal if it conveys no information from Bob to Alice. We show that all semicausal complete-measurement superoperators are semi localizable, and we establish a general criterion for semicausality. In the multipartite case, we observe that a measurement superoperator that projects onto the eigenspaces of a stabilizer code is localizable.

Deletion of 8p: a report of a child with normal intelligence

The case is presented of a female infant with a distal deletion of 8p (8p23.1 --> pter) whose development was monitored over a 5-year period from 12 months of age. Although previous literature has suggested that 8p deletion is associated with mild to moderate intellectual disability, the child reported here has normal intelligence. Despite initial delays in gross motor and language skills, cognitive development (assessed with the Bayley Scales of Infant Development) and intellectual ability (measured on the Stanford-Binet Intelligence Scale) were within average range. It is argued that the small number of previous case reports may have created a misleading impression of intellectual development in individuals with distal deletions of 8p.

The ratio of messenger RNA levels of receptor activator of nuclear factor kappa B ligand to osteoprotegerin correlates with bone remodeling indices in normal human cancellous bone but not in osteoarthritis

skeletal disease. Bone remodeling is initiated by osteoclastic resorption followed by osteoblastic formation of new bone. Receptor activator of nuclear factor KB ligand (RANKL) is a newly described regulator of osteoclast formation and function, the activity of which appears to be a balance between interaction with its receptor RANK and with an antagonist binding protein osteoprotegerin (OPG). Therefore, we have examined the relationship between the expression of RANKL, RANK, and OPG and indices of bone structure and turnover in human cancellous bone from the proximal femur. Bone samples were obtained from individuals with osteoarthritis (OA) at joint replacement surgery and from autopsy controls. Histomorphometric analysis of these samples showed that eroded surface (ES/BS) and osteoid surface (OS/BS) were positively associated in both control (p < 0.001) and OA (p < 0.02), indicating that the processes of bone resorption and bone formation remain coupled in OA, as they are in controls. RANKL, OPG, and RANK messenger RNA, (mRNA) were abundant in human cancellous bone, with significant differences between control and OA individuals. In coplotting the molecular and histomorphometric data, strong associations were found between the ratio of RANKL/OPG mRNA and the indices of bone turnover (RANKL/OPG vs. ES/BS: r = 0.93, p < 0.001; RANKL/OPG vs. OS/BS: r = 0.80, p < 0.001). These relationships were not evident in trabecular bone from severe OA, suggesting that bone turnover may be regulated differently in this disease. We propose that the effective concentration of RANKL is related causally to bone turnover.

Determination of reference values for glucose tolerance, insulin tolerance, and insulin sensitivity tests in clinically normal cats

Objective-To determine reference values and test variability for glucose tolerance tests (GTT), insulin tolerance tests (ITT), and insulin sensitivity tests (IST) in cats, Animals-32 clinically normal cats. Procedure-GTT, ITT, and IST were performed on consecutive days. Tolerance intervals tie, reference values) were calculated as means +/- 2.397 SD for plasma glucose and insulin concentrations, half-life of glucose (T-1/2glucose), rate constants for glucose disappearance (K-glucose and K-itt), and insulin sensitivity index (S-l). Tests were repeated after 6 weeks in 8 cats to determine test variability. Results-Reference values for T-1/2glucose, K-glucose, and fasting plasma glucose and insulin concentrations during GTT were 45 to 74 minutes, 0.93 to 1.54 %/min, 37 to 104 mg/dl, and 2.8 to 20.6 muU/ml, respectively. Mean values did not differ between the 2 tests. Coefficients of variation for T-1/2glucose, K-glucose, and fasting plasma glucose and insulin concentrations were 20, 20, 11, and 23%, respectively. Reference values for K-itt were 1.14 to 7.3%/min, and for S-l were 0.57 to 10.99 x 10(-4) min/muU/ml. Mean values did not differ between the 2 tests performed 6 weeks apart, Coefficients of variation for K-itt and S-l were 60 and 47%, respectively. Conclusions and Clinical Relevance-GTT, ITT, and IST can be performed in cats, using standard protocols. Knowledge of reference values and test variability will enable researchers to better interpret test results for assessment of glucose tolerance, pancreatic beta -cell function, and insulin sensitivity in cats.

A soluble form of CD83 is released from activated dendritic cells and B lymphocytes, and is detectable in normal human sera

CD83 is an inducible glycoprotein expressed predominantly by dendritic cells (DC) and B lymphocytes. Expression of membrane CD83 (mCD83) is widely used as a marker of differentiated/ activated DC but its function and ligand(s) are presently unknown. We report the existence of a soluble form of CD83 (sCD83). Using both a sCD83-specific ELISA and Western blotting, we could demonstrate the release of sCD83 by mCD83(+) B cell and Hodgkin's disease-derived cell lines, but not mCD83(-) cells. Inhibition of de novo protein synthesis did not affect the release of sCD83 during short-term (2 h) culture of cell lines although mCD83 expression was significantly reduced, suggesting sCD83 is generated by the release of mCD83. Isolated tonsillar B lymphocytes and monocyte-derived DC, which are mCD83(low), released only low levels of sCD83 during culture. However, the differentiation/activation of these populations both up-regulated mCD83 and increased sCD83 release significantly. Analysis of sera from normal donors demonstrated the presence of low levels (121 +/- 3.6 pg/ml) of circulating sCD83. Further studies utilizing purified sCD83 and the analysis of sCD83 levels in disease may provide clues to the function and ligand(s) of CD83.

Detection and description of non-linear interdependence in normal multichannel human EEG data

Objectives: This study examines human scalp electroencephalographic (EEG) data for evidence of non-linear interdependence between posterior channels. The spectral and phase properties of those epochs of EEG exhibiting non-linear interdependence are studied. Methods: Scalp EEG data was collected from 40 healthy subjects. A technique for the detection of non-linear interdependence was applied to 2.048 s segments of posterior bipolar electrode data. Amplitude-adjusted phase-randomized surrogate data was used to statistically determine which EEG epochs exhibited non-linear interdependence. Results: Statistically significant evidence of non-linear interactions were evident in 2.9% (eyes open) to 4.8% (eyes closed) of the epochs. In the eyes-open recordings, these epochs exhibited a peak in the spectral and cross-spectral density functions at about 10 Hz. Two types of EEG epochs are evident in the eyes-closed recordings; one type exhibits a peak in the spectral density and cross-spectrum at 8 Hz. The other type has increased spectral and cross-spectral power across faster frequencies. Epochs identified as exhibiting non-linear interdependence display a tendency towards phase interdependencies across and between a broad range of frequencies. Conclusions: Non-linear interdependence is detectable in a small number of multichannel EEG epochs, and makes a contribution to the alpha rhythm. Non-linear interdependence produces spatially distributed activity that exhibits phase synchronization between oscillations present at different frequencies. The possible physiological significance of these findings are discussed with reference to the dynamical properties of neural systems and the role of synchronous activity in the neocortex. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved.

Nuclear RelB(+) cells are found in normal lymphoid organs and in peripheral tissue in the context of inflammation, but not under normal resting conditions

Differentiated dendritic cells (DC) have been identified by the presence of nuclear RelB (nRelB) and HLA-DR, and the absence of CD20 or high levels of CD68, in lymph nodes and active rheumatoid arthritis synovial tissue. The current studies aimed to identify conditions in which nRelB is expressed in human tissues, by single and double immunohistochemistry of formalin-fixed peripheral and lymphoid tissue. Normal peripheral tissue did not contain nRelB(+) cells. nRelB(+) DC were located only in T- or B-cell areas of lymphoid tissue associated with normal organs or peripheral tissues, including tonsil, colon, spleen and thymus, or in association with T cells in inflamed peripheral tissue. Inflamed sites included skin delayed-type hypersensitivity reaction, and a wide range of tissues affected by autoimmune disease. Nuclear RelB(+) -HLA-DR- follicular DC were located in B-cell follicles in lymphoid organs and in lymphoid-like follicles of some tissues affected by autoimmune disease. Lymphoid tissue T-cell areas also contained nRelB(-) -HLA-DR+ cells, some of which expressed CD123 and/or CD68. Nuclear RelB(+) cells are found in normal lymphoid organs and in peripheral tissue in the context of inflammation, but not under normal resting conditions.

Spermine modulation of the glutamate(NMDA) receptor is differentially responsive to conantokins in normal and Alzheimer's disease human cerebral cortex

The pharmacology of the N -methyl-d-aspartate (NMDA) receptor site was examined in pathologically affected and relatively spared regions of cerebral cortex tissue obtained at autopsy from Alzheimer's disease cases and matched controls. The affinity and density of the [H-3]MK-801 binding site were delineated along with the enhancement of [H-3]MK-801 binding by glutamate and spermine. Maximal enhancement induced by either ligand was regionally variable; glutamate-mediated maximal enhancement was higher in controls than in Alzheimer's cases in pathologically spared regions, whereas spermine-mediated maximal enhancement was higher in controls in areas susceptible to pathological damage. These and other data suggest that the subunit composition of NMDA receptors may be locally variable. Studies with modified conantokin-G (con-G) peptides showed that Ala(7)-con-G had higher affinity than Lys(7)-con-G, and also defined two distinct binding sites in controls. Nevertheless, the affinity for Lys(7)-con-G was higher overall in Alzheimer's brain than in control brain, whereas the reverse was true for Ala(7)-con-G. Over-excitation mediated by specific NMDA receptors might contribute to localized brain damage in Alzheimer's disease. Modified conantokins are useful for identifying the NMDA receptors involved, and may have potential as protective agents.