Morphology of the ventral frontal cortex in schizophrenia: relationship with social dysfunction.

BACKGROUND: Studies have reported premorbid as well as postonset social dysfunction in schizophrenia. This impairment has also been observed to emerge after lesions in the ventral aspect of the frontal cortex (i.e., straight gyrus and orbitofrontal cortex). METHODS: Magnetic resonance imaging scans were obtained from 45 male patients with schizophrenia and 45 matched control subjects. Cortical gray matter volume and surface area were determined for the ventral frontal cortex (VFC), subdivided into the orbitofrontal cortex (OFC) and the straight gyrus (SG). RESULTS: The global measures of gray matter volume and surface area in the VFC was not significantly different between patients and control subjects; however, there was a regional difference, with the right SG volume and surface area being smaller in patients compared with control subjects. Volume of the VFC had an inverse correlation with measurements of both premorbid and postdiagnosis social function. The smaller the gray matter in these regions, the greater the social dysfunction. There was no relationship between morphology of this brain region and any other clinical variable. CONCLUSIONS: Morphology of the VFC is directly related to abnormal social function in schizophrenia, including measures of social dysfunction that predate the onset of illness.     

Hepatitis C virus envelope components alter localization of hepatocyte tight junction-associated proteins and promote occludin retention in the endoplasmic reticulum

Hepatocyte tight junctions (TJ) play key roles in characteristic liver functions, including bile formation and secretion. Infection by hepatitis C virus (HCV) may cause alterations of the liver architecture and disruption of the bile duct, which ultimately can lead to cholestasis. Herein, we employed the HCV replicon system to analyze the effect of HCV on TJ organization. TJ-associated proteins occludin, claudin-1, and Zonula Occludens protein-1 (ZO-1) disappeared from their normal localization at the border of adjacent cells in Huh7 clones harboring genomic but not subgenomic replicons expressing only the nonstructural proteins. Furthermore, cells containing genomic replicons showed a cytoplasmic accumulation of occludin in the endoplasmic reticulum (ER). TJ-associated function, measured as FITC-dextran paracellular permeability, of genomic replicon-containing cells, was also altered. Interestingly, clearance of the HCV replicon by interferon-alpha (IFN-alpha) treatment and by short hairpin RNA (shRNA) significantly restored the localization of TJ-associated proteins. Transient expression of all HCV structural proteins, but not core protein alone, altered the localization of TJ-associated proteins in Huh7 cells and in clones with subgenomic replicons. Confocal analysis showed that accumulation of occludin in the ER partially co-localized with HCV envelope glycoprotein E2. E2/occludin association was further confirmed by co-immunoprecipitation and pull-down assays. Additionally, using a cell culture model of HCV infection, we observed the cytoplasmic dot-like accumulation of occludin in infected Huh7 cells. CONCLUSION: We propose that HCV structural proteins, most likely those of the viral envelope, promote alterations of TJ-associated proteins, which may provide new insights for HCV-related pathogenesis.     

Optical anisotropy of alcian blue-stained acid glycosaminoglycans

Optical anisotropy as dispersion of birefringence (DB) (birefringence studied for light of different wavelengths) and linear dichroism (LD) (selective absorption of polarized light) in stained substrates reflects their macromolecular orientation states. Birefringence interference colors of alcian blue (AB)-stained glycosaminoglycans (GAG) and glycoconjugates observed with polarization microscopy have been found to vary, although their staining characteristics under unpolarized light are practically the same. We investigated the optical anisotropy of GAG-AB and some glycoconjugate-AB complexes used as standards, to provide a basis for interpreting results for AB-stained materials in situ. Filamentous preparations of hyaluronic acid (HA), chondroitinsulfates, proteoglycans, and a mucus sulfoglycoconjugate were studied. Anomalous DB (birefringence sign changing with the wavelength of the incident light) was generally observed, but LD was seen only in the AB-HA complex. LD simultaneous to anomalous DB characteristics on the AB-HA complex were assumed to be caused by a maximally oriented helical conformation of the HA. For the other AB-GAG studied, the optical anisotropic characteristics were suggestive of some degree of folding of their chains into a tertiary structure. The profiles of the anomalous DB curves for the AB-stained sulfoglycoconjugate differed from those of the other materials, probably due to different organization of its dye-binding sites.     

The dynamic relationship between insight and suicidal behavior in first episode psychosis patients over 3-year follow-up

Studies have established the high risk of suicide in first episode psychosis (FEP). Between 15% and 26% of FEP patients attempt suicide at least once before their first contact with psychiatric services and 2–5% die from suicide. Also, many patients with schizophrenia spectrum disorders lack insight into having a mental disorder. However, the relationship between insight changes and suicidal behavior in FEP remains poorly understood. In the present study information about suicidal behavior over a 3 years period was available on a cohort of 397 FEP patients, of whom 270 were assessed in the three dimensions of insight (into mental illness, the need for treatment, and the social consequences) at baseline, 1 and 3 years after treatment initiation. Survival analyses examined time to suicidal behavior in relation to (i) insight at baseline, (ii) the closest insight measure to the suicide attempt, and (iii) changes in insight during the follow-up. No associations were found between baseline insight dimensions and time to suicidal behavior. However, poor insight at the evaluation closest to the suicide attempt was associated with an increased risk of suicide. Stability of insight did not affect the risk of suicidal behavior, while changes in either direction were linked with an increased risk of suicidal behavior, particularly worsening insight. Insight in psychosis is a dynamic concept and we demonstrated the relationship between insight and suicide risk to be equally dynamic. Poor insight seems to increase the risk, especially when insight levels change. Repeated insight assessment to detect change from early psychosis may play a role in suicide prevention.     

Reduced thalamic volume in first-episode non-affective psychosis: correlations with clinical variables, symptomatology and cognitive functioning

Structural studies have inconsistently shown the presence of thalamic volume differences in patients with schizophrenia. However, only a few studies have examined the relation between thalamic structure and clinical and cognitive variables in early phases of the illness. Thalamic volumes in right-handed minimally treated first episode patients with non-affective psychosis (N=61) relative to those of right-handed healthy comparison subjects (N=40) were measured. Thalamic volumes in the right and left hemispheres and total thalamic volume were automatically segmented and analyzed using BRAINS2. Analysis of covariance was used to control for intracranial volume. Clinical symptoms were assessed by total scores of BPRS, SAPS and SANS. The relationship between three cognitive dimensions (verbal learning and memory, speed processing/executive functioning and sustained attention/vigilance), and thalamic volume was evaluated. The impact of the duration of untreated illness, untreated psychosis and prodrome period in thalamic morphometry was also explored. Right, left, and total thalamic volumes of the patients with non-affective psychosis were significantly smaller than those of the healthy subjects. Larger thalamic volumes were associated with an earlier age of onset, a poorer cognitive functioning and a more severe negative symptomatology. Thalamic volumetric differences between patients with non-affective psychosis and healthy controls are already present at early phases of the illness. However, further investigations are warranted to fully clarify the relationship between those structural anomalies and clinical and cognitive outcomes.     

Root trunk height as a risk factor for periodontal furcation involvement in maxillary first molars: an in vitro study

The aim of this study was to correlate the root trunk height from the furcation openings on the buccal, mesial and distal surfaces to the cemento-enamel junction in upper first permanent molars in human beings with risk for periodontal disease progression. One hundred extracted maxillary first molars were used. Reference points and demarcations were determined from the entrance of the buccal (F1), mesial (F2) and distal (F3) furcations to the cemento-enamel junction in millimeters. The mean distances found were 3.50 mm, 4.44 mm and 4.26 mm for the buccal, mesial and distal furcations, respectively, in relation to the cemento-enamel junction. The statistical analyses were Student's t-test and Chi-square (X2). With periodontal disease progression, the buccal furcation presents a greater compromising risk due to its proximity to the cemento-enamel junction, while the mesial furcation is the most distant, comprising a lesser risk.     

Value of ultrasound-guided core biopsy in the diagnosis of malignant lymphoma

PURPOSE: Ultrasound-guided core needle biopsy for the diagnosis and management of malignant lymphomas is controversial and has not been accepted as an alternative to surgical biopsy. We investigate the clinical usefulness of this procedure in a large series of patients. METHODS: Over a 5-year period (2000-2004), ultrasound-guided core needle biopsies were performed in 102 malignant lymphomas. Five diagnostic categories were considered: large B-cell lymphomas (LBCL), small B-cell lymphomas (SBCL), Hodgkin's disease (HD), T cell lymphomas, and miscellaneous. Surgical excisional biopsy of the node was performed in 47 cases (46.1%) for diagnostic confirmation. RESULTS: The overall diagnostic accuracy of ultrasound-guided core needle biopsy was 88.2% (90/102). SBCL (39), LBCL (36), HD (15), T cell lymphomas (5), and miscellaneous (7) [including T cell-rich B cell (2), natural killer cell (1), Burkitt's lymphoma (1), and non-Hodgkin's lymphoma of the B cell type, NOS (3)] were correctly diagnosed. Three HDs, 1 natural killer cell lymphoma, 1 follicular lymphoma, and 1 LBCL were not correctly diagnosed. The core needle biopsy did not yield tumor tissue in 6 cases. CONCLUSIONS: Ultrasound-guided core needle biopsy is effective in the diagnosis of malignant lymphomas and can be used as the first diagnostic approach in selected clinical situations.