Effects of cholesterol and apolipoprotein E on retinal abnormalities in ApoE-deficient mice.

PURPOSE: To examine the pathologic changes in the retina of apolipoprotein E (apoE)-deficient mice fed a high-cholesterol diet. METHODS: ApoE-deficient mice (ApoE) were maintained on either regular mouse chow (ApoE-R) or a high-cholesterol diet (ApoE-C) for 25 weeks. Age-matched control C57BL/6J mice (C57) were also maintained on either regular mouse chow (C57-R) or a cholesterol-containing diet (C57-C). Retinal function was assessed by dark-adapted electroretinography (ERG). The eyes were embedded, sectioned, and analyzed by histologic and immunohistochemical methods, as well as by light and transmission electron microscopy. RESULTS: After the 25-week feeding period, ERG tracings of ApoE-C mice revealed significant increases of a- and b-wave implicit times when compared with the C57-R group of mice. In addition, there were reductions in oscillatory potential (OP) amplitudes in the ApoE-C group. However, a- and b-wave amplitudes appeared to be unchanged among the four groups of mice. Light microscopic examination of the retinas showed that compared with control C57-R mice, ApoE-C mice had significantly lower cell numbers in the inner and outer nuclear layers (85.1% +/- 4.6%, P < 0.05 and 81.4% +/- 3.7%, P < 0.01 of C57-R controls, respectively). Transmission electron microscopy of apoE-deficient mice revealed cells of the inner nuclear layer with condensation of nuclear chromatin and perinuclear vacuolization in focal areas. Bruch's membrane was also found to be thicker, and its elastic lamina appeared disorganized and discontinuous. Immunohistochemistry demonstrated diminished or no immunoreactivity for carbonic anhydrase II and calretinin in the retinal layers of apoE-deficient mice. CONCLUSIONS: Overall, there were increasing abnormalities of retinal function and cellular morphology among the four groups of mice in the order of C57-R < C57-C < ApoE-R < ApoE-C. These findings suggest that apoE and/or cholesterol play an important role in retinal function.

Newborn baboon serum lacks natural anti-pig xenoantibody.

Discordant xenotransplantation represents an attractive alternative to allotransplantation in light of the shortage of donor organs currently available for cardiac allotransplantation. Unfortunately, discordant xenotransplantation is still limited by hyper-acute rejection, a process thought to be mediated by natural anti-xenodonor antibody. Based on data that cytotoxic natural xenoantibodies are IgM in nature, we postulated that natural xenoantibodies may be absent from newborn serum. Baboon sera were collected from infant baboons. Pooled adult baboon sera were used as controls. A whole cell ELISA was performed to determine the binding of xenoantibodies to pig aortic endothelial cells and pig lymphocytes. The cytotoxicity of both adult and newborn baboon sera to pig aortic endothelial cells was measured by a MTT (3-(4,5-dimethyl-thiazoyl-2-y) 2,5 diphenyl-tetrazolium bromide) assay. Newborn baboon sera demonstrated very low levels of binding of natural IgM xenoantibodies to pig endothelial cells and lymphocytes, whereas natural IgM xenoantibodies from adult baboon sera bound significantly to both pig aortic endothelial cells and lymphocytes. IgG natural antibodies in both adult and newborn sera bound to pig endothelial cells and pig lymphocytes. The MTT assay demonstrated high levels of cytotoxicity to pig endothelial cells from adult baboon sera and very low levels of cytotoxicity from newborn baboon sera. In this study, newborn baboon sera were demonstrated to be free of natural IgM xenoantibodies to pig endothelial cells and lymphocytes. Although natural anti-pig IgG antibodies were present in newborn sera, newborn baboon sera lack cytotoxicity to pig target cells. These findings suggest that IgM is the more important xenoantibody and that hyperacute rejection of discordant cardiac xenografts may be avoidable in the newborn.

Interpersonal problems, attachment styles, and outcome in brief dynamic psychotherapy.

The Inventory of Interpersonal Problems (IIP) has been used to identify dysfunctional patterns in interpersonal interactions. Interpersonal problems can be organized in two dimensions, and the two-dimensional space can be divided into eight equal sectors (octants). Subscales of the IIP describe each of these octants. The instrument has been used to identify (a) interpersonal problems that are discussed most often in a brief dynamic psychotherapy and (b) problems that are treated most easily. The results show that problems in the "exploitable" octant improve most frequently, whereas problems in the "dominating," "vindictive," and "cold" octants do not improve as readily. Attachment styles in adulthood were examined (following a model proposed by Bowlby), and different attachment styles were found to correspond to different types of interpersonal problems. Finally, these variables were related to the ability to describe other people clearly. The article also discusses implications for brief dynamic psychotherapy.

Psychodynamic formulation, consensual response method, and interpersonal problems.

We describe a new method for aggregating psychodynamic formulations of independent clinicians. 15 patients (10 female and 5 male, aged 23-41) were interviewed before they began brief dynamic psychotherapy. Different panels of 8 formulators (drawn from a pool of 72 psychodynamic clinicians with 10-38 years of clinical experience) observed each videotaped interview and wrote individual formulations. The text of each formulation was divided into thought-units, and thought-units that occurred 3 or more times were combined into a final consensual formulation. (One case was formulated twice to demonstrate the replicability of the method). Other clinical raters then read each consensual formulation and judged, for a list of interpersonal problems, whether each problem was apt to be distressing for that patient. The raters were very successful in predicting which problems were later discussed in treatment. Predictions were best for formulations with a high proportion of interpersonal content.

A method for establishing reliability of statements from psychodynamic case formulations.

The authors describe a method for assessing the reliability of statements derived from psychodynamic case formulations. By reducing a narrative formulation into a series of distinct statements and rating their relevance to a particular patient, they obtained good interjudge reliabilities.