CAG repeat polymorphism within the KCNN3 gene is a significant contributor to susceptibility to anorexia nervosa: a case-control study of female patients and several ethnic groups in the Israeli Jewish population.

The human small-conductance Ca(2+)-activated potassium channel gene KCNN3 has been involved in mechanisms underlying neuronal function and plasticity. A multiallelic CAG repeat polymorphism within the KCNN3 has been associated with schizophrenia and bipolar disorder. We have previously reported in a family-based study that longer CAG repeats are preferentially transmitted to patients with anorexia nervosa (AN). The present study extends the analysis of KCNN3 allele distribution to a larger series of AN female patients and control groups, incorporating information on ethnicity and co-morbidities associated with AN. The data analysis is presented while considering separately the two alleles of each individual, namely a minor (shorter) and a major (longer) allele. This study has found that the KCNN3 allele distribution in the general Israeli population does not differ significantly in at least four Jewish ethnic groups of Ashkenazi, North African, Iraqi, and Yemenite origin. These have been used as control groups in a matched case-control analysis that has demonstrated a significant over-representation of KCNN3 alleles with longer CAG repeats among AN patients (P < 0.001 for the major allele and P = 0.035 for allele sum). Under dichotomization, a significantly higher prevalence of the L allele (>19 repeats) has been observed among AN patients (P < 0.001). While considering AN and co-morbid phenotypes, a tendency towards longer (L) alleles has been observed in the subset of patients with obsessive-compulsive disorder (OCD) co-morbidity. These findings further implicate KCNN3 as a significant contributor to predisposition to AN.     

Conformation of Replicated Segments of Chromosome Fibres in Human S-phase Nucleus

Recent statistical analysis of the folding of G0/G1 chromosomes using fluorescence in situ hybridization (FISH) allowed development of a random walk/giant loop model of chromosome structure. According to this model there are two levels of organization of G0/G1 chromosome fibres. On the first level, the fibres are arranged in giant loops several Mbp in size, and within each loop the fibres are randomly folded. On the second level, the loop attachment sites form a chromosome backbone that also shows random folding. Newly replicated segments of mammalian chromosomes may be directly visualized at high resolution in S-phase nuclei using immunofluorescent methods and appear as worm-like fibres. In our earlier study, we analysed conformation of the fibres in human cells blocked for 16 h at the G1/S boundary with 5- fluorodeoxyuridine (FdU) and then released into S-phase by the addition of a DNA prec ursor. However, long treatment of cells with FdU induces very short replicons and may promote apoptosis. In this study we analysed conformation of the fibres in normally proliferating human cells that had not been blocked with FdU for a long time. It has been found that replicated chromosome fibres visualized just after 2 h of incubation of the cells with a non-radioactively labelled DNA precursor behave as flexible polymer chains without major constraints, and that their local conformation in the range of several microns of their contour length may be considered as random. Confocal analysis of human X chromosomes visualized in HeLa cells using FISH with a specific painting probe shows that in S-phase the chromosomes occupy distinct nuclear territories and their apparent size does not differ from that in non-S-phase cells. This observation indicates that the second level of chromosome organization also exists in S-phase chromosomes. It appears, theref ore, that the random walk/giant loop model developed earlier for G0/G1 chromosomes is also valid for S-phase chromosomes.     

Public–Private Collaboration in Health and Human Service Delivery: Evidence from Community Partnerships

The collaboration among public–private partnerships that applied to the Community Care Network (CCN) demonstration program of the Hospital Research and Educational Trust is examined. These partnerships link broad-based community coalitions with health and human service providers in efforts to improve community health and local service delivery. Although they willingly collaborated in identifying community health needs, coordinating services, and reporting to the community, partnership participants showed less alacrity in joining forces to reduce redundancy and increase efficiency. Such patterns suggest that organizations might best profit from working together on activities that maintain existing power relations and that have the potential to add prestige and attract new clients. Collaboration in these areas may be essential to building a foundation of trust that leads to future cooperation in more sensitive areas.     

Biochemical markers of compliance in the Physicians' Health Study

The Physicians' Health Study is a randomized, double-blind, placebo-controlled trial using a 2 x 2 factorial design to test the effects of low-dose aspirin on risk of cardiovascular disease and beta-carotene supplementation on the incidence of cancer. To evaluate self-reported compliance with assigned treatment, we measured serum thromboxane B2, which is decreased after aspirin use, and plasma beta-carotene in samples of study participants drawn from three geographic locations in three different time periods. Thromboxane B2 levels were markedly lower in those assigned to aspirin (median = 63.5 pg/mL) than in those given aspirin placebo (median = 3,600 pg/mL, P less than .0001). Similarly, those assigned to beta-carotene had significantly higher levels (median = 1,176 ng/mL) than those given placebo (median = 306 ng/mL, P less than .0001). In addition, there was a highly significant positive correlation between levels of these biochemical markers and the self-reports of compliance (r = 0.65 for thromboxane B2 and r = 0.69 for beta-carotene, P less than .0001). These findings support the validity of the self-reported compliance in the Physicians' Health Study.     

The organization of trigeminotectal and trigeminothalamic neurons in rodents: a double-labeling study with fluorescent dyes

Retrogradely transported fluorescent dyes (fast blue and diamidino-dihydrochloride yellow) were used to compare the distributions of trigeminofugal neurons that project to the superior colliculus and/or the thalamus in three rodent species. The objective was to determine what the projection and collateralization patterns of these trigeminofugal pathways are and whether they are similar among different species. In each anesthetized animal, one dye was injected into the superior colliculus and the other into the topographically congruent area of the thalamus. Counts of the numbers of yellow, blue, and double-labeled neurons were made throughout the trigeminal complex: principalis, pars oralis, pars interpolaris, and pars caudalis. Trigeminothalamic projections were similar in each of the rodent species studied. The densest concentration of retrogradely labeled neurons was in principalis, with substantially fewer neurons in pars interpolaris, and fewer still in pars oralis and pars caudalis. These neurons were generally small and tended to have round or fusiform somata. A common pattern was also noted among the three species for trigeminotectal neurons. Most trigeminotectal projections originated from neurons in pars interpolaris, somewhat fewer from pars oralis, and the fewest from principalis and pars caudalis. These neurons tended to be the largest in each subdivision and were often multipolar. Following paired injections of the tracers, double-labeled neurons were scattered throughout the sensory trigeminal complex and had morphologies characteristic of single-labeled trigeminotectal neurons. Although comparatively few double-labeled neurons were observed in any species, most of those seen were restricted to the ventrolateral portion of pars interpolaris, a position that corresponds to the representation of the vibrissae. These data indicate that, regardless of the rodent species, the vast majority of labeled trigeminal neurons project either to the superior colliculus or the thalamus, but not to both targets. This might be expected on the basis of the very different behavioral roles these structures play. On the other hand, a subpopulation of trigeminal neurons exists (mainly in pars interpolaris) that does project to both the superior colliculus and the thalamus, perhaps because both structures require some of the same somatosensory information to perform their behavioral functions.     

Direct measurement of the conduction velocity of single motor axons in man

The conduction velocity (CV) of single motor axons was measured in the ulnar and median nerve. Stimuli of submaximal intensities were delivered at the wrist and at the elbow using surface electrodes. The responses of single motor units were recorded by tungsten or steel microelectrodes. Changes of the stimulus intensity and of the position of the stimulation electrodes and subtraction of the responses frequently allowed the potential of the same motor unit to be identified following stimulation at both sites and to calculate its axonal CV. In all individuals, axonal CV's from the low to the high velocity range (40 to 63 m/s) could be measured. The method may provide a new approach to the investigation of various disorders of the peripheral nerve.     

Impairment of polymorphonuclear leukocyte function and metabolic control of diabetes.

OBJECTIVE--In this study, ingestion of Staphylococcus aureus and "bacteria killing" (BK) were measured to evaluate polymorphonuclear leukocyte (PMN) phagocytic functions and chemiluminescence response (CL) to phorbol-myristic acetate (PMA) as respiratory burst activity with regard to metabolic control parameters in diabetic patients. RESEARCH DESIGN AND METHODS--PMN phagocytic functions were assessed in 40 diabetic patients, all receiving insulin and in poor metabolic control, with 3H-thymidine-labeled Staphylococcus aureus in a modified radiometric assay. Bacteria killing was determined by pure-plate counting of surviving bacteria (colony-forming units [cfu]) and luminol-enhanced CL in response to PMA as a measure of respiratory burst. PMN function data were correlated to HbA1 as parameter of recent metabolic control. RESULTS--PMN of diabetic patients showed a significant reduction in Staphylococcus aureus (50.7 +/- 4.1%) and BK (29.4 +/- 4.2%) compared with healthy nondiabetic control subjects (76.6 +/- 4.6% and 16.3 +/- 3.1%, respectively, P less than 0.001), and PMN CL response was markedly reduced in diabetic patients also. Linear regression analysis showed a highly significant negative correlation of HbA1 versus Staphylococcus aureus (r = -0.67, P = 0.001) and a positive correlation for BK (r = 0.73, P less than 0.001). This was also true for CL, although this did not reach statistical significance (P = 0.06). CONCLUSIONS--The data obtained demonstrate impaired PMN phagocytic functions and CL response in diabetic patients. These findings suggest inhibitory effects of elevated glucose concentrations on PMNs, a possible role of protein glycosylation for impairing PMN function, thus contributing in part to altered host defense.     

Association between childhood trauma and physical disorders among adults in the United States

BACKGROUND: The goal of this investigation was to determine the association between self-reported childhood trauma and physical disorders among adults in the United States. METHOD: Data were drawn from the National Comorbidity Survey (N=5877). Multiple logistic regression analyses were used to determine the associations between childhood physical abuse, sexual abuse, and childhood neglect and the likelihood of specific physical disorders among adults. RESULTS: Childhood physical abuse, sexual abuse and neglect were associated with a statistically significantly increased risk of a wide range of physical illnesses during adulthood. After adjusting for demographic characteristics, lifetime anxiety and depressive disorders, alcohol and substance dependence, and all types of trauma: results showed that childhood physical abuse was associated with increased risk of lung disease (OR= 1.5 (1.1, 2.2)), peptic ulcer (OR= 1.5 (1.03, 2.2)) and arthritic disorders (OR= 1.5 (1.1, 2.2)); childhood sexual abuse was associated with increased risk of cardiac disease (OR = 3.7 (1.5, 9.4)); and childhood neglect was associated with increased risk of diabetes (OR=2 2 (1.1, 4.4)) and autoimmune disorders (OR =4.4 (1.7, 11.6)). CONCLUSIONS: Consistent with previous work, these results suggest that self-reported childhood trauma is associated with increased risk of a range of physical illnesses during adulthood. Future research that includes replication of these findings using prospectively assessed physical and mental disorders with objectively measured biological data using a longitudinal design, including other known risk factors for these diseases and more detailed information on specific forms of abuse, is needed to understand the potential mechanisms of these links.