Context-Processing Deficits in Schizotypal Personality Disorder.

Research suggests that schizotypal personality disorder (SPD) is a part of the spectrum of schizophrenia-related illnesses. This article hypothesizes that a deficit in the representation and maintenance of context is a core cognitive disturbance in schizophrenia and that SPD individuals should demonstrate context-processing deficits. To test this hypothesis, the authors administered 3 versions of their AX-CPT task, designed to assess context processing, to 35 healthy controls and 26 individuals with DSM-IV SPD. They also administered working memory and selective attention tasks. SPD individuals displayed context representation deficits similar to those found in schizophrenia but did not show the same additional deficits in context maintenance. Context processing was strongly associated with working memory and selective attention performance in the SPD individuals. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Effect of moderate to very low fat defined formula diets on serum lipids in healthy subjects

Serum total cholesterol, high density lipoprotein (HDL) cholesterol, and triglyceride levels were studied in healthy male and female subjects consuming for one-week periods a diet of conventional food (CF) providing 42% of energy as fat, principally butter fat, and then in random order nutritionally complete, defined formula diets of moderate (32%) to very low (1%) fat content. Compared to CF, the formula with 32% of energy as corn oil lowered serum cholesterol by 25% and the ratio of total to HDL-cholesterol by 13%. Low (9%) and very low (1–3%) fat formulas reduced HDL-cholesterol by as much as 40%, raised the total: HDL-cholesterol ratio by about 20% and raised serum triglyceride levels by as much as 100%. When low and very low fat formulas were ingested for three weeks, these effects persisted although maximal responses occurred during the first week. These results demonstrated that a moderate fat formula diet with a high P/S ratio had a more favorable effect on serum lipid levels than various low fat formulas. Low fat conventional food diets should be studied in long-term controlled metabolic experiments before such diets are recommended to the general population for coronary heart disease or cancer prevention.     

Ambulatory subcutaneous internal sphincterectomy]

The internal anal sphincterotomy operation represents the best therapy for the treatment of those anal lesions, above all anal fissures, which cause hypertrophy and spasms of the internal anal sphincter. The Authors report their experience of 253 operations of internal subcutaneous sphincterotomy carried out between 1989 and 1995 under local anaesthesia in the outpatient clinic. The excellent results achieved prove that the procedure can easily be carried out under local anaesthesia in an outpatient clinic and, therefore, it is preferable to the surgical technique of isolation of the internal sphincter, not only for its practicality but also for the improved results.     

Activation of alphav beta3 integrin on human osteoclast-like cells stimulates adhesion and migration in response to osteopontin

Integrins mediate cell adhesion and can induce different cellular responses, including changes in intracellular pH, changes and oscillation in intracellular free calcium, and protein phosphorylation on tyrosine. During bone resorption, the integrin alphav beta3 regulates adhesion of osteoclasts to bone extracellular matrix proteins, such us osteopontin (Opn). Adhesion via alphav beta3 is followed by osteoclast polarization onto the bone surface and by the onset of bone resorption. To characterize these events at the molecular level, we investigated the state of activation of alphav beta3 on the human osteoclast-like cell line GCT23 using the monoclonal antibody AP5 which binds to and can induce, under low calcium conditions, activated alphav beta3. By flow cytometry, approximately 50% of alphav beta3 on the surface of the osteoclast-like cell line GCT23 was reactive with AP5 and was therefore in the activated state. Incubation with AP5 in the presence of low calcium concentrations increased activated alphav beta3 to 90-100%. Activation of alphav beta3 increased the efficiency of GCT23 adhesion to Opn by 2-fold. Furthermore, haptotactic migration on Opn was also enhanced about 40% compared to control. We propose that changes in the activation state of alphav beta3 may be a regulation point for osteoclasts during bone resorption.     

Alagille syndrome: family studies

Alagille syndrome (AGS) is one of the major forms of chronic liver disease in childhood with severe morbidity and a mortality of 10 to 20%. It is characterised by cholestasis of variable severity with paucity of interlobular bile ducts and anomalies of the cardiovascular system, skeleton, eyes, and face. Previous studies suggest a wide variation in the expression of the disease and a high incidence of new mutations. To determine more accurately the rate of new mutations and to develop criteria for detecting the disorder in parents we systematically investigated parents in 14 families with an affected child. Clinical examination was supplemented by liver function tests, echocardiography, radiographic examination of the spine and forearm, ophthalmological assessment, and chromosome analysis. Six parents had typical anomalies in two or more systems pointing to the presence of autosomal dominant inheritance. Systematic screening of parents for the features defined in this study should improve the accuracy of genetic counselling.     

MR monitoring of focused ultrasonic surgery of renal cortex: experimental and simulation studies

The aim of the study was to test the hypothesis that magnetic resonance (MR) imaging-guided and -monitored noninvasive ultrasonic surgery can be performed in highly perfused tissues from outside the body. A simulation study was performed to evaluate the optimal sonication parameters. An MR-compatible positioning device was then used to manipulate a focused ultrasound transducer in an MR imager, which was used to sonicate kidneys of five rabbits at various power levels and different durations. Temperature elevation during sonication was monitored with a T1-weighted spoiled gradient-echo sequence. The simulation study demonstrated that a sharply focused transducer and relatively short sonication times (30 seconds or less) are necessary to prevent damage to the overlying skin and muscle tissue, which have a much lower blood perfusion rate than kidney. The experiments showed that the imaging sequence was sensitive enough to show temperature elevation during sonication, thereby indicating the location of the beam focus. Histologic evaluations showed that kidney necrosis could be consistently induced without damage to overlying skin and muscle. The study demonstrated that highly perfused tissues such as the renal cortex can be coagulated from outside the body with focused ultrasound and that MR imaging can be used to guide and monitor this surgery.     

Depressive symptomatology in maritally discordant women and men: The role of individual and relationship variables.

Marital discord and depressive symptomatology have repeatedly been found to be associated, but little is known about variables that influence this relationship. Data were collected from 139 couples seeking marital therapy, and analyses were conducted separately by gender. For wives, lower problem-solving ability, physical aggression by the partner, and 1 relationship belief predicted depressive symptomatology after the variance due to marital discord was removed in regression analyses. In addition to these predictors, less spouse-specific assertiveness, unemployment, and 1 other relationship belief were associated with depressive symptomatology for women after the variance due to marital discord was removed in partial correlation analyses. For men, only lower problem-solving ability added to the prediction of depressive symptomatology. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

EGF/EGF-R system and benign breast disease during and following the treatment of gynaecological pathologies with an analogue of LH-RH

Clinical and pathological changes of the mammary gland have been studied in 64 women affected by symptomatic Benign Breast Disease (BBD) coexisting with endometriosis or uterine leiomyomata. These patients were rendered hypoestrogenic by subcutaneous administration of the LH-RH analogue Goserelin depot [D-ser (tBu)6 Aza-Gly10-GnRH (ICI118630)] performed every 28 days, for six months. They were evaluated clinically and ultrasonographically before and after treatment to find possible changes of BBD as well as of endometriosis or uterine leiomyomata. Mammary biopsies were performed before and after treatment in all the patients to study the changes of EGF-R expression. Results showed that clinical improvement is accompanied with a reduction of EGF-R expression.     

Rorschach cognitive developmental indices of mentally retarded persons: a comparison with scores on Wechsler Intelligence Scale for children-revised

The complete mechanism by which pathogenic mtDNA mutations cause cellular pathophysiology and in some cases cell death is unclear. Oxidant stress is especially toxic to excitable nerve and muscle cells, cells that are often affected in mitochondrial disease. The sensitivity of cells bearing the LHON, MELAS, and MERRF mutations to oxidant stress was determined. All were significantly more sensitive to H2O2 exposure than their nonmutant cybrid controls, the order of sensitivity was MELAS > LHON > MERRF > controls. Depletion of Ca2+ from the medium protected all cell lines from oxidant stress, consistent with the hypothesis that death induced by oxidant stress is Ca(2+)-dependent. A potential downstream target of Ca2+ is the mitochondrial permeability transition, MPT, which is inhibited by cyclosporin A. Treatment of MELAS, LHON, and MERRF cells with cyclosporin A caused significant rescue from oxidant exposure, and in each case significantly greater rescue of mutant than control cells. The pronounced oxidant-sensitivity of mutant cells, and their protection by Ca2+ depletion and CsA, has potential implications for both the pathophysiological mechanism and therapy of these mitochondrial genetic diseases.     

Nuclear Receptor Nur77 Controls Cardiac Fibrosis through Distinct Actions on Fibroblasts and Cardiomyocytes

Fibrosis is a hallmark of adverse cardiac remodeling, which promotes heart failure, but it is also an essential repair mechanism to prevent cardiac rupture, signifying the importance of appropriate regulation of this process. In the remodeling heart, cardiac fibroblasts (CFs) differentiate into myofibroblasts (MyoFB), which are the key mediators of the fibrotic response. Additionally, cardiomyocytes are involved by providing pro-fibrotic cues. Nuclear receptor Nur77 is known to reduce cardiac hypertrophy and associated fibrosis; however, the exact function of Nur77 in the fibrotic response is yet unknown. Here, we show that Nur77-deficient mice exhibit severe myocardial wall thinning, rupture and reduced collagen fiber density after myocardial infarction and chronic isoproterenol (ISO) infusion. Upon Nur77 knockdown in cultured rat CFs, expression of MyoFB markers and extracellular matrix proteins is reduced after stimulation with ISO or transforming growth factor–β (TGF-β). Accordingly, Nur77-depleted CFs produce less collagen and exhibit diminished proliferation and wound closure capacity. Interestingly, Nur77 knockdown in neonatal rat cardiomyocytes results in increased paracrine induction of MyoFB differentiation, which was blocked by TGF-β receptor antagonism. Taken together, Nur77-mediated regulation involves CF-intrinsic promotion of CF-to-MyoFB transition and inhibition of cardiomyocyte-driven paracrine TGF-β-mediated MyoFB differentiation. As such, Nur77 provides distinct, cell-specific regulation of cardiac fibrosis.