Identification of MMS19 domains with distinct functions in NER and transcription.

Nucleotide excision repair (NER) and RNA polymerase II (Pol II) transcription are essential cellular processes which are intimately intertwined. They share an indispensable multiprotein complex, TFIIH, and impairments in either process can impact the efficiency of the other. Like TFIIH, MMS19 is required for NER and Pol II transcription, but its precise role in each process is unknown. We showed previously that the human MMS19 gene originates multiple splice variants, some of which may encode distinct MMS19 protein isoforms. Here we characterize a novel MMS19 transcript and demonstrate for the first time that MMS19 splice variants are conserved across species and are functionally distinct. Expression of human MMS19 splice variants in mms19-deleted yeast cells produced unique patterns of thermosensitivity and ultraviolet radiation-sensitivity that point to three MMS19 structural domains with distinct in vivo functions. MMS19 polypeptides lacking domain A are able to fulfill the role of full-length MMS19 in NER but not in transcription. MMS19 polypeptides lacking part of domain B are efficient in transcription but not in NER. MMS19 polypeptides lacking domain C (HEAT repeats) are unable to fulfill either function. Our data suggest that the MMS19 HEAT repeat domain is essential for MMS19 function in NER and transcription, while domains A and B, within MMS19 N-terminus, modulate the balance between DNA repair and transcription. Our results highlight the functional significance of MMS19 transcripts and the possible contribution of MMS19 isoforms to regulate the switch between NER and transcription. Furthermore, our work associates for the first time specific protein domains with MMS19's role in NER and transcription.

Laparoscopic nephron-sparing surgery in a Jehovah's Witness patient.

An obese 76-year-old woman with type II diabetes, hypertension, coronary artery disease, and gastroesophageal reflux was found to have a 6-cm lower-pole mass in a solitary functional right kidney. Because her religious beliefs prohibited blood transfusion, minimally invasive surgery--a laparoscopic partial nephrectomy--was performed, with a good result. Minimally invasive surgery, perhaps with administration of erythropoietin, iron-dextran, or both, is often a good option for severely anemic patients or those whose religious beliefs are opposed to transfusion. Methods of minimizing blood loss intraoperatively are reviewed.

Profile of H1N1 infection in a tertiary care center.

BACKGROUND: A novel swine origin influenza virus (H1N1) is spreading worldwide and threatens to become pandemic.H1N1 critical illness mostly affects young patients and is often fatal. AIM: The aim of the present study is to evaluate the clinical characteristic of H1N1 infection in a tertiary care hospital. MATERIALS AND METHODS: A total of 92 nasal and pharyngeal swabs from suspected cases of swine flu were processed by real time reverse transcriptase polymerase chain reaction (rRT-PCR). RESULT: Twenty(21.73%) were positive of which two were treating physicians and five (25%) patients expired. CONCLUSIONS: The age group of positive cases of H1N1 was between 21 and 30 years and age group of patients who died ranged from 40 to 45 year. This overview indicates that although the majority of hospitalized persons infected with novel influenza A (H1N1) recovered without complications, certain patients had severe and prolonged disease. It was also noted that 2009 influenza A (H1N1) infection - related clinical illness predominantly affects young patients. All hospitalized patients with novel influenza A (H1N1) infection should be monitored carefully and treated with antiviral therapy. Mandatory vaccination of health-care workers is especially important in emerging pandemic.

Cerebral oxygenation in major pediatric trauma: its relevance to trauma severity and outcome.

INTRODUCTION: Trauma is the commonest cause of death in the pediatric population, which is prone to diffuse primary brain injury aggravated by secondary insults (eg, hypoxia, hypotension). Standard monitoring involves intracranial pressure (ICP) and cerebral perfusion pressure, which do not reflect true cerebral oxygenation (oxygen delivery [Do(2)]). We explore the merits of a brain tissue oxygen-directed critical care guide. METHODS: Sixteen patients with major trauma (Injury Severity Score, >16/Pediatric Trauma Score [PTS], <7) had partial pressure of brain tissue oxygen (Pbto(2)) monitor (Licox; Integra Neurosciences, Plainsboro, NJ) placed under local anesthesia using twist-drill craniostomy and definitive management of associated injuries. Pbto(2) levels directed therapy intensity level (ventilator management, inotrops, blood transfusion, and others). Patient demographics, short-term physiological parameters, Pbto(2), ICP, Glasgow Coma Score, trauma scores, and outcomes were analyzed to identify the patients at risk for low Do(2). RESULTS: There were 10 males and 6 females (mean age, 14 years) sustaining motor vehicle accident (14), falls (1), and assault (1), with a mean Injury Severity Score of 36 (16-59); PTS, 3 (0-7); and Revised Trauma Score, 5.5 (4-11). Eleven patients (70%) had low Do(2) (Pbto(2), <20 mm Hg) on admission despite undergoing standard resuscitation affected by fraction of inspired oxygen, Pao(2), and cerebral perfusion pressure (P = .001). Eubaric hyperoxia improved cerebral oxygenation in the low-Do(2) group (P = .044). The Revised Trauma Score (r = 0.65) showed moderate correlation with Pbto(2) and was a significant predictor for low Do(2) (P = .001). In patients with Pbto(2) of less than 20 mm Hg, PTS correlated with cerebral oxygenation (r = 0.671, P = .033). The mean 2-hour Pbto(2) and the final Pbto(2) in survivors were significantly higher than deaths (21.6 vs 7.2 mm Hg [P = .009] and 25 vs 11 mm Hg [P = .01]). Although 4 of 6 deaths were from uncontrolled high ICP, PTS and 2-hour low Do(2) were significant for roots for mortality. CONCLUSIONS: Pbto(2) monitoring allows for early recognition of low-Do(2) situations, enabling appropriate therapeutic intervention.