ATM: a mediator of multiple responses to genotoxic stress

The ATM protein kinase is the product of the gene responsible for the pleiotropic recessive disorder ataxia-telangiectasia. ATM-deficient cells show enhanced sensitivity and greatly reduced responses to genotoxic agents that generate DNA double strand breaks (DSBs), such as ionizing radiation and radiomimetic chemicals, but exhibit normal responses to DNA adducts and base modifications induced by other agents. Therefore, DSBs are most likely the predominant signal for the activation of ATM-mediated pathways. Identification of the ATM gene triggered extensive research aimed at elucidating the numerous functions of its large multifaceted protein product. While ATM has both nuclear and cytoplasmic functions, this review will focus on its roles in the nucleus where it plays a central role in the very early stages of damage detection and serves as a master controller of cellular responses to DSBs. By activating key regulators of multiple signal transduction pathways, ATM mediates the efficient induction of a signaling network responsible for repair of the damage, and for cellular recovery and survival.     

A prospective randomized controlled study of the effect of short coincubation of gametes during insemination on zona pellucida thickness

A prospective, randomized study was conducted to evaluate the thickness of zona pellucida (ZP) after brief or standard exposure of human oocytes to spermatozoa, and to determine the correlation between ZP thickness, fertilization rate and embryo quality. The mean ZP thickness 48?h after insemination was found to be significantly less in fertilized oocytes than in non-fertilized oocytes in all treated groups (13.72?±?3.0?µm and 15.08?±?2.5?µm, respectively; p?<?0.007). Zona pellucida thickness correlated positively with embryo quality. Brief exposure of gametes was found to influence ZP thickness. The ZP was significantly thinner after brief and intracytoplasmic sperm injection (ICSI) exposure of oocytes to spermatozoa than after standard in vitro fertilization (IVF). The mean ZP thickness 24 and 48?h after fertilization was significantly greater in standard IVF (16.43?±?2.8?µm and 15.22?±?2.7?µm, respectively) than in either the brief exposure or ICSI groups (12.78?±?2.4?µm and 13.01?±?3.5?µm vs. 13.46?±?2.2?µm and 13.16?±?2.4?µm; p?<?0.0001).     

Hepatomegaly following short-term high-dose steroid therapy

Children treated with large doses of corticosteroids were found to develop hepatomegaly within a few days. No relationship could be established between the condition for which steroids were given and the liver enlargement. Liver biopsy was thought to be indicated, and thus was performed in three children because of diagnostic uncertainty. The light and electron microscopic examinations revealed normal liver architecture, without edema, sinusoid engorgement, or inflammatory changes. The hepatocytes were distended by increased amounts of glycogen. In a pattern reminiscent of some glycogen storage diseases, mitochondria and other cytosol components were displaced toward the cell membrane or around the nucleus, which occasionally contained glycogen. Moderate sinusoidal compression, interhepatocytic free glycogen particles, and mild increase in lipid droplets were also found. It is concluded that the hepatomegaly noted in patients given short-term, high-dosage steroid therapy is due to excessive glycogen accumulation within parenchymal cells. This finding is in accordance with observations in animals, as well as with biochemical studies demonstrating hepatocytic glycogen deposition after steroid therapy. Being benign and reversible, early hepatomegaly following administration of high-dose corticosteroids should not influence the initial therapeutic plan required by the basic disease.     

In vivo occipital-frontal temperature-gradient in schizophrenia patients and its possible association with psychopathology: a magnetic resonance spectroscopy study

BACKGROUND: Accumulating data suggest that schizophrenia patients' mental status might be modulated by their core/brain temperature. Hence, we intended to assess in vivo brain temperature (Tb) of schizophrenia patients vs. healthy subjects and to evaluate its potential association with patients' mental status. METHODS: Absolute values of Tb were measured in 9 neuroleptic-treated schizophrenia patients and 10 healthy comparison subjects using 1H magnetic resonance spectroscopy (MRS). Values were extracted by measuring the chemical shift between the peaks of water and N-acetyl-aspartate in the 1H MRS spectra. RESULTS: A substantial (about 1.1 degrees C) and significantly higher occipital-frontal temperature-gradient was found in the schizophrenia patients compared to the healthy controls (1.27 degrees C vs. 0.18 degrees C; p=0.032). Furthermore, a trend was found between the above mentioned occipital-frontal temperature-gradient in the schizophrenia patients and the severity of their psychopathology, as assessed by the total Positive and Negative Syndrome Scale (PANSS) scores (r=0.61; p=0.08). CONCLUSIONS: Our findings corroborate previous results indicating putative correlation between core/brain temperature and the mental status of schizophrenia patients, emphasizing the possible role of within patients decreased frontal temperature and a significant occipital-frontal temperature-gradient as modulators of psychopathology. In addition, the MRS technique used for brain temperature assessment seems to be a potential non-invasive method to assess in vivo absolute Tb in schizophrenia.     

Importance of phenotypic and molecular characterization for identification of a neuroepithelioma tumor cell line, NUB-20

A neuroblastic-like cell line (NUB-20) was derived from a case of histopathologically diagnosed metastatic neuroblastoma. The metastatic tumor and nude mouse heterotransplant resembled neuroblastoma by histological criteria, in contrast to the primary tumor, which was differentially classified as Ewing's sarcoma. However, the cell line demonstrated a unique phenotype in culture with respect to morphology, immunohistochemical markers, and sensitivity to a battery of differentiation modulators. These characteristics, together with the presence of a chromosomal translocation (11;22),(q24;q12) and amplification with enhanced expression of the c-myc protooncogene rather than N-myc, established this tumor as neuroepithelioma. Neuroepithelioma is a tumor type distinct from, but related to, neuroblastoma in its development from the neural crest lineage. These results emphasize the growing importance of cytogenetic and molecular markers in the classification and characterization of human tumors.     

Parenting styles and eating disorder pathology

Our objective was to investigate the association between parenting style and eating disorder symptoms in patients treated in an intensive outpatient center for eating disorders. The study design is a cross-sectional survey set in a community-based facility for eating disorders. Participants included 53 families, including 32 with a child meeting the DSM-IV criteria for anorexia nervosa, 18 for bulimia nervosa, and 3 diagnosed ED-NOS. Data was collected using the Parental Authority Questionnaire (PAQ), the Eating Disorders Inventory-2 (EDI-2) and the Eating Attitudes Test (EAT-26). Significant, negative correlations were found between drive for thinness scores and body dissatisfaction scores and the patient's perception of the father as authoritative. Total patient EDI score was significantly and positively correlated with patient's perception of the father as authoritarian and inversely correlated with her perception of him as authoritative. These results emphasize the importance of fathers’ role in the eating disorder pathology, a relatively untapped area of research.     

Erratum: The choices,choosing model of quality of life: description and rationale

International Journal of Geriatic Psychiatry 2009; 24: 90–95 DOI: 10.1002/gps.2110 If has come to our attention that this Research Article was published with an incorrect SUMMARY. We now publish below, the entire SUMMARY as first intended.     

Emotional reactivity and debilitating beliefs during hospitalization predict future adjustment to first myocardial infarction in men

Research efforts are being made to identify personality and cognitive variables predictive of poor adjustment following myocardial infarction. Sixty-two male patients were examined after a first and uncomplicated myocardial infarction to determine whether dispositional emotional reactivity and debilitating beliefs measured during hospitalization can predict work engagement, social activities involvement, and ambulation/independence six months later. A structural model with direct paths between emotional reactivity, debilitating beliefs, and the above outcomes, as well as partial mediation of emotional distress and illness preoccupation, was tested using the CALIS procedure. The model explained 33%, 48% and 82% of the variance in the three outcomes, respectively. Work engagement was indirectly related through emotional distress to earlier emotional reactivity and debilitating beliefs. Social activities involvement was both directly and indirectly related through emotional distress to debilitating beliefs; and also indirectly related through emotional distress to emotional reactivity. Ambulation/independence was directly and negatively related to debilitating beliefs. Prolonged emotional distress was predicted by emotional reactivity and debilitating beliefs. Illness preoccupation turned out to be an independent outcome that was positively related to emotional reactivity. Thus, measuring dispositional emotional reactivity and debilitating beliefs at the hospitalization stage may be helpful in detecting patients at risk of poor future adjustment.