A pilot study of personality pathology in patients with anorexia nervosa: modifiable factors related to outcome after hospitalization.

OBJECTIVE: To assess improvement in aspects of personality in patients hospitalized with anorexia nervosa (AN) and its relationship to improved depression, body mass index (BMI), and eating disorder outcome after treatment. METHOD: Twenty females hospitalized with AN completed intake and discharge assessments of BMI, depression and eating disorder severity, as well as personality pathology with the Minnesota Multiphasic Personality Inventory (MMPI-2) and the Revised NEO Personality Inventory (NEO PI-R). Clinical outcome for a subset of patients at 1-year post-hospitalization was determined. RESULTS: The only factor that predicted better versus worse outcome at 1-year post-hospitalization was change in Low Self-Esteem (LSE) from the MMPI-2. Improved LSE from admission to discharge predicted remission at 1-year post-hospitalization, while worsening LSE predicted relapse. Regardless of outcome, NEO PI-R Neuroticism remained pathologically elevated in AN patients during hospitalization. DISCUSSION: Pathological levels of neuroticism may represent a vulnerability factor for AN. In contrast, self-esteem appears to be a modifiable factor that predicts outcome following hospitalization, and may be an important target for treatment.

The putative tumor suppressor LRP1B, a novel member of the low density lipoprotein (LDL) receptor family, exhibits both overlapping and distinct properties with the LDL receptor-related protein.

The low density lipoprotein receptor-related protein-deleted in tumor (LRP1B, initially referred to as LRP-DIT) was cloned and characterized as a candidate tumor suppressor. It is a new member of the low density lipoprotein receptor gene family. Its overall domain structure and large size (approximately 600 kDa) are similar to LRP and suggest that it is a multifunctional cell surface receptor. Herein, we characterize a series of ligands for the receptor using cell lines that stably express it as a domain IV minireceptor (mLRP1B4). Ligands of LRP including receptor-associated protein, urokinase plasminogen activator, tissue-type plasminogen activator, and plasminogen activator inhibitor type-1 each demonstrate binding, internalization, and degradation via mLRP1B4. Interestingly, the kinetics of ligand endocytosis is distinctly different from that of LRP, with LRP1B exhibiting a markedly diminished internalization rate. In addition, tissue expression analysis reveals that the LRP1B gene is expressed in brain, thyroid, and salivary gland. These studies thus extend the physiological roles of members of the LDL receptor family.

Dissection of receptor folding and ligand-binding property with functional minireceptors of LDL receptor-related protein.

The LDL receptor-related protein (LRP) is a large, multifunctional endocytic receptor that binds and endocytoses a variety of structurally and functionally distinct ligands. LRP contains four putative ligand-binding domains. However, only domains II, III and IV, but not domain I, bind the receptor-associated protein (RAP), a molecular chaperone and universal antagonist for LRP. In order to dissect the function of RAP in LRP folding and to examine the ligand-binding properties of LRP, we generated LRP minireceptors that represent each of the four putative ligand-binding domains (termed mLRP1, mLRP2, mLRP3 and mLRP4, respectively). We found that proper folding and trafficking of mLRP2, mLRP3, mLRP4, but not mLRP1, is facilitated by coexpression of RAP. When these mLRPs were stably expressed in Chinese Hamster Ovary cells that lack the endogenous LRP, we found that each of these receptors was processed and traffics through the secretory pathway. Cell surface expression of these minireceptors was quantitatively examined by flow cytometric analyses. Using these minireceptor cell lines to map the ligand-binding domains, we found that although the majority of LRP ligands bind to both domain II and domain IV, Pseudomonas exotoxin A utilizes only domain IV for its binding to LRP. We conclude that while domains II and IV of LRP share many ligand-binding properties, each of the putative ligand-binding domains of LRP is unique in its contribution to ligand binding.

An electrical model for the cytoplasmic calcium wave in fertilized eggs.

The calcium wave subsequent to fertilization of the egg is analyzed interms of an electrical equivalent circuit. The circuit consists of aswitch, capacitor, an inductor, and a resistor. The switch symbolizes aseries of chemical reactions initiated by the sperm the lead to thedevelopment of the calcium wave. Its closure signifies the onset of thecalcium wave. The capacitor and inductor represent the endoplasmicreticulum. The capacitive component of the endoplasmic reticulum controlsthe release of calcium ions while the inductive component regulates thesequestration of clacium ions. The resistor represents the inductor andcytoplasm and has very low resistance. The analysis of the circuit showsthat the period of the calcium oscillations is proportional to the size ofthe egg. It agrees with the measurements on various types of eggs.

Dynamic infrared imaging of cardiac pacemaker induction and cortical muscle contractions of embryonic avian heart.

The dynamic nature of electromagnetic (EM) pacemaker induction of cardiac tissue contractions in cultured embryonic avian heart was analyzed with noninvasive real time infrared (IR) imaging at normal physiological conditions. This technique was used to visualize the endogenous sarcomeric Ca2+ oscillation induced cortical IR-EM radiation within an 8-12 micron IR emission spectra. The results reported here establishes the fact that cardiac energetics produce topographical IR-EM radiation that can be visualized directly without invasive dyes or external light sources to noninvasively study the mechanisms of striated muscle tissue morphogenesis. Since IR microscopy capitalizes on imaging the inherent radiation from biological molecules in tissue, no external light sources are needed to reflect a visual spectrum. These findings provide the framework for future noninvasive investigations and characterizations of the endogenous energetics in living cells.

Tumour necrosis factor alpha production by rat blood and its ex vivo pharmacological modulation.

Rat blood was investigated as a suitable test system for the discovery of inhibitors of tumour necrosis factor alpha (TNF alpha) biosynthesis. Lipopolysaccharide (LPS) caused a concentration- and time-dependent stimulation of TNF alpha production by heparinised rat blood with peak levels (1000-5000 U/ml; L929 bioassay) at 6 h. Bioactive material was neutralised with a polyclonal rabbit anti-murine TNF alpha antibody which cross-reacts with rat TNF alpha. Dexamethasone, pentoxifylline and denbufylline inhibited TNF alpha production with IC50s of 6.0 +/- 2.0 nM, 20.6 +/- 8.00 microM and 138.0 nM, respectively. When rats were dosed p.o. with dexamethasone or pentoxifylline or i.p. with denbufylline and 1.5 h later TNF alpha production was assessed ex vivo by LPS-stimulated blood, a dose-related inhibition of TNF alpha production occurred with ID50s of approximately 0.08, 250.0 and 5.0 mg/kg, respectively. These results demonstrate that rat blood provides a useful test system for the detection and ex vivo evaluation of inhibitors of TNF alpha biosynthesis.

Production of TNF alpha by LPS-stimulated murine, rat and human blood and its pharmacological modulation.

Tumour necrosis factor alpha (TNF alpha) has been reported to play a key role in the pathogenesis of sepsis and chronic inflammatory diseases, including rheumatoid arthritis and atherosclerosis, suggesting that agents which inhibit TNF alpha production may have therapeutic utility for the treatment of such conditions. Production of TNF alpha by LPS (lipopolysaccharide)-stimulated murine, rat and human heparinized blood was investigated. LPS (1-100 micrograms/ml) caused a similar concentration- and time-dependent stimulation of TNF alpha production by rat and human blood, achieving levels of 750-5000 U/ml (L929 bioassay) at 6 h. In contrast, TNF alpha production by LPS-stimulated murine blood was poor and variable (0-150 U/ml). Dexamethasone and pentoxifylline caused a concentration-dependent inhibition of TNF alpha production by LPS-stimulated human and rat blood with IC50s of 0.26 +/- 0.05 and 73.0 +/- 26.4 microM for human and 5.7 +/- 1.8 nM and 20.6 +/- 8.0 microM for rat blood, respectively. Therefore, LPS-stimulated rat and human, but not murine, blood are suitable systems for the detection and evaluation of inhibitors of TNF alpha production.