G protein ß5-ATM complexes drive acetaminophen-induced hepatotoxicity.

Excessive ingestion of the common analgesic acetaminophen (APAP) leads to severe hepatotoxicity. Here we identify G protein ß5 (Gß5), elevated in livers from APAP overdose patients, as a critical regulator of cell death pathways and autophagic signaling in APAP-exposed liver. Liver-specific knockdown of Gß5 in mice protected the liver from APAP-dependent fibrosis, cell loss, oxidative stress, and inflammation following either acute or chronic APAP administration. Conversely, overexpression of Gß5 in liver was sufficient to drive hepatocyte dysfunction and loss. In hepatocytes, Gß5 depletion ameliorated mitochondrial dysfunction, allowed for maintenance of ATP generation and mitigated APAP-induced cell death. Further, Gß5 knockdown also reversed impacts of APAP on kinase cascades (e.g. ATM/AMPK) signaling to mammalian target of rapamycin (mTOR), a master regulator of autophagy and, as a result, interrupted autophagic flux. Though canonically relegated to nuclear DNA repair pathways, ATM also functions in the cytoplasm to control cell death and autophagy. Indeed, we now show that Gß5 forms a direct, stable complex with the FAT domain of ATM, important for autophosphorylation-dependent kinase activation. These data provide a viable explanation for these novel, G protein-independent actions of Gß5 in liver. Thus, Gß5 sits at a critical nexus in multiple pathological sequelae driving APAP-dependent liver damage.

Profile of postmortem cases conducted at a morgue of a tertiary care hospital in Kolkata.

A record based cross-sectional study of postmortems performed at the mortuary attached to the forensic medicine and toxicology department of RG Kar Medical College and Hospital from March 2008 to February 2009 comprising 1900 cases was conducted to determine the sociodemographic profile and to assess the nature and cause of such deaths. Bodies of 5 foetuses were decomposed which were excluded from the study. Out of a total of 1895 postmortems analysed, 23 autopsies were performed of limbs where the subjects were alive. Out of 1872 cases in 325 (17.4%) the manner of death was natural, whereas in 1547 cases (82.6%) it was unnatural. Accidents, suicides, homicides and undetermined deaths were 63.1%, 29.8%, 2.8% and 4.3% respectively. Among the natural deaths, evidence of pulmonary tuberculosis and coronary heart disease was found in 141 (43.4%) and 124 (38.2%) cases respectively. Burn injuries (22.6%) were the most common cause of unnatural deaths and occurred in 77.4% females. Rail track injuries and road traffic injuries were responsible for 21.9% and 14% of unnatural deaths. Hanging, poisoning and self-immolation were responsible for 48.4%, 28.9% and 19.7% of suicidal deaths respectively.

Extranodal non-Hodgkin's lymphoma presenting as an ovarian mass.

An 8-year-old female presented with an abdominal lump. A ultrasonography showed a heterogeneous, mainly solid space-occupying lesion with few cystic components and irregular margin in both adnexae measuring 10.5 x 5.2 x 3.5 cm and 9.2 x 4.8 x 3.0 cm. The tumors were removed by exploratory laparotomy and the histopathological report was primary NHL of the ovary. The uterus and cervix were healthy and there was no tumor extension or omental deposit. The patient was referred for chemotherapy.

R study of suicide with special reference to endometrial study in female individuals.

A study was conducted at Bankura Sammilani Medical College, Bankura, West Bengal, on suicide victims whose postmortem examination was performed between 1st January, 2003 and 31st December, 2003. Various epidemiological, aetiological and other related factors were studied. There were 42 males (36.21%) and 74 females (63.79%) among the total victims (n=116). Torture by in-laws for dowry was found to be the commonest predisposing factor for suicide (n=34; 29.31%). Consumption of poison was the commonest method (n=48; 41.38%). Incidence of suicide was at its peak during the month of May (n=18; 15.52%). Endometriums of female subjects of child-bearing age (n=60) were studied under microscope and most of them (n=47) were seen to be in secretory phase at the time of commitment of suicide.