The U.S. Food and Drug Administration's role in improving radiation dose management for medical X-ray imaging devices.

The U.S. Food and Drug Administration (FDA) has been concerned with minimizing the unnecessary radiation exposure of people for half a century. Manufacturers of medical X-ray imaging devices are important partners in this effort. Medical X-ray imaging devices are regulated by FDA under both its electronic product regulations andits medical device regulations. FDA also publishes guidance documents that represent FDA's current thinking on a topic and provide a suggested or recommended approach to meet the requirements of a regulation or statute. FDA encourages manufacturers to develop medical devices that conform to voluntary consensus standards. Use of these standards is a central element of FDA's system to ensure that all medical devices marketed in the U.S. meet safety and effectiveness requirements. FDA staff participate actively in the development and maintenance of these standards, often advancing or introducing new safety and dose management requirements. Use of voluntary consensus standards reduces the amount of time necessary to evaluate a premarket submission and reduces the burden on manufacturers. FDA interacts with industry and other stakeholders through meetings with industry groups, public meetings, public communications, and through the development of voluntary consensus standards. In these interactions, FDA staff introduce new concepts for improving the safety of these devices and provide support for similar initiatives from professional organizations. FDA works with all stakeholders to achieve its mission of protecting and promoting the public health.

Clinical importance of duodenal recesses with special reference to internal hernias.

INTRODUCTION: The detailed knowledge of the peritoneal recesses has great significance with respect to internal hernias. The recesses are usually related to rotation and adhesion of abdominal viscera to the posterior abdominal wall and/or the presence of retroperitoneal vessels which raises the serosal fold. The duodenal recesses are usually related to the 3rd and 4th parts of the duodenum. Internal hernias with respect to these recesses are difficult to diagnose clinically and usually noticed at the time of laparotomy. So, the knowledge of these recesses can be valuable to abdominal surgeons. MATERIAL AND METHODS: The present study was conducted in 100 cases including 10 cadavers, 45 post mortem cases and 45 cases undergoing laparotomy. RESULTS: We found superior and inferior duodenal recesses in 28% and 52% respectively, paraduodenal in 12%, mesentericoparietal in 3%, retroduodenal in 2% and duodenojejunal in 18% of cases. Two abnormal duodenojejunal recesses were found, one on the right (instead of the left) of the abdominal aorta, and in the other the opening was directed upwards instead of downwards. The incidence of internal hernias was 3%. CONCLUSIONS: Thus it was observed that there is low incidence of superior and inferior duodenal recesses, and high incidence of paraduodenal recess. The abnormal recesses might be due to malrotation of the gut. In laparotomy cases, the internal hernia was noticed when the abdomen was opened for intestinal obstruction. The incidence of internal hernia was found to be high.

Right Sided Sigmoid Colon and Redundant Loop of Descending Colon with Its Embryological Correlation and Clinical Significance.

Anatomical variations of colon are mostly developmental and can lead to variety of acute and chronic pathological conditions. So it becomes important to recognize and understand the importance of clinical implications of such anomalies to benefit surgeons, clinical geneticists and research community. We describe two cases of right sided sigmoid colon and long descending colon which had two segments: vertical and horizontal. The mesentery of ascending and descending colon was retained. This mesentery along with the mesentery of transverse colon was continuous with the mesentery of small intestine. There were variations in blood vessels supplying these anomalous colons. The findings of this study may be helpful to make surgeons and radiologists aware about different varieties of presentations while undertaking an investigative or surgical procedure in this area like sigmoidoscopy, percutaneous cecostomy and anterior transperitoneal aproach of kidney to avoid colon puncture.

Allosteric Activation of Bacterial Swi2/Snf2 (Switch/Sucrose Non-fermentable) Protein RapA by RNA Polymerase: BIOCHEMICAL AND STRUCTURAL STUDIES.

Members of the Swi2/Snf2 (switch/sucrose non-fermentable) family depend on their ATPase activity to mobilize nucleic acid-protein complexes for gene expression. In bacteria, RapA is an RNA polymerase (RNAP)-associated Swi2/Snf2 protein that mediates RNAP recycling during transcription. It is known that the ATPase activity of RapA is stimulated by its interaction with RNAP. It is not known, however, how the RapA-RNAP interaction activates the enzyme. Previously, we determined the crystal structure of RapA. The structure revealed the dynamic nature of its N-terminal domain (Ntd), which prompted us to elucidate the solution structure and activity of both the full-length protein and its Ntd-truncated mutant (RapAΔN). Here, we report the ATPase activity of RapA and RapAΔN in the absence or presence of RNAP and the solution structures of RapA and RapAΔN either ligand-free or in complex with RNAP. Determined by small-angle x-ray scattering, the solution structures reveal a new conformation of RapA, define the binding mode and binding site of RapA on RNAP, and show that the binding sites of RapA and σ(70) on the surface of RNAP largely overlap. We conclude that the ATPase activity of RapA is inhibited by its Ntd but stimulated by RNAP in an allosteric fashion and that the conformational changes of RapA and its interaction with RNAP are essential for RNAP recycling. These and previous findings outline the functional cycle of RapA, which increases our understanding of the mechanism and regulation of Swi2/Snf2 proteins in general and of RapA in particular. The new structural information also leads to a hypothetical model of RapA in complex with RNAP immobilized during transcription.

Racial variation on articular surface of talus (astragalus) in North Indian population.

Articular morphology, especially of the lower limb, can be modified by various stresses on bone like adoption of bipedal gait and erect posture resulting in variations of the skeleton. Effects of variations in posture like squatting, which are a part of lifestyle of certain populations, were studied on 147 tali of North Indian population and examined for differences with those from other geographic regions. The modifications were classified into nine types. The lateral squatting facet was the most frequently found variation (65.9%), the medial, combined and continuous squatting facets being 8.2%, 2.04% and 4.1%, respectively. Lateral (32.7%), medial (27.2%) and continuous (4.7%), trochlear extensions, and extensions of medial (39.4%) and lateral (12.9%) articular facets were also observed in the population studied. The findings of the present study were important markers which could help in determining the race of unidentified bones.

Crystal structures of Parasponia and Trema hemoglobins: differential heme coordination is linked to quaternary structure.

Hemoglobins from the plants Parasponia andersonii (ParaHb) and Trema tomentosa (TremaHb) are 93% identical in primary structure but differ in oxygen binding constants in accordance with their distinct physiological functions. Additionally, these proteins are dimeric, and ParaHb exhibits the unusual property of having different heme redox potentials for each subunit. To investigate how these hemoglobins could differ in function despite their shared sequence identity and to determine the cause of subunit heterogeneity in ParaHb, we have measured their crystal structures in the ferric oxidation state. Furthermore, we have made a monomeric ParaHb mutant protein (I43N) and measured its ferrous/ferric heme redox potential to test the hypothesized link between quaternary structure and heme heterogeneity in wild-type ParaHb. Our results demonstrate that TremaHb is a symmetric dimeric hemoglobin similar to other class 1 nonsymbiotic plant hemoglobins but that ParaHb has structurally distinct heme coordination in each of its two subunits that is absent in the monomeric I43N mutant protein. A mechanism for achieving structural heterogeneity in ParaHb in which the Ile(101(F4)) side chain contacts the proximal His(105(F8)) in one subunit but not the other is proposed. These results are discussed in the context of the evolution of plant oxygen transport hemoglobins, and other potential functions of plant hemoglobins.

Micromanagement of the mitochondrial apoptotic pathway by p53.

It is now well established that p53 is the primary arbiter of stress-response and the principal barrier to neoplastic processes at the cellular level. Perhaps the most potent weapon in p53's tumor suppressive arsenal is apoptosis, enacted as a last resort when all other remedies are exhausted. Initially, the mechanism was thought to be simply activation or repression of Bcl-2 family members by p53. More recently, evidence of a more rapid pathway emerged whereby p53 physically interacts with Bcl-2 family members to tip the balance toward apoptosis. This review details the multiple levels of regulation of mitochondrially-directed apoptosis by p53, including recent findings of how p53 translocation is regulated.

Structure and reactivity of hexacoordinate hemoglobins.

The heme prosthetic group in hemoglobins is most often attached to the globin through coordination of either one or two histidine side chains. Those proteins with one histidine coordinating the heme iron are called "pentacoordinate" hemoglobins, a group represented by red blood cell hemoglobin and most other oxygen transporters. Those with two histidines are called "hexacoordinate hemoglobins", which have broad representation among eukaryotes. Coordination of the second histidine in hexacoordinate Hbs is reversible, allowing for binding of exogenous ligands like oxygen, carbon monoxide, and nitric oxide. Research over the past several years has produced a fairly detailed picture of the structure and biochemistry of hexacoordinate hemoglobins from several species including neuroglobin and cytoglobin in animals, and the nonsymbiotic hemoglobins in plants. However, a clear understanding of the physiological functions of these proteins remains an elusive goal.

Trema and parasponia hemoglobins reveal convergent evolution of oxygen transport in plants.

All plants contain hemoglobins that fall into distinct phylogenetic classes. The subset of plants that carry out symbiotic nitrogen fixation expresses hemoglobins that scavenge and transport oxygen to bacterial symbiotes within root nodules. These "symbiotic" oxygen transport hemoglobins are distinct in structure and function from the nonoxygen transport ("nonsymbiotic") Hbs found in all plants. Hemoglobins found in two closely related plants present a paradox concerning hemoglobin structure and function. Parasponia andersonii is a nitrogen-fixing plant that expresses a symbiotic hemoglobin (ParaHb) characteristic of oxygen transport hemoglobins in having a pentacoordinate ferrous heme iron, moderate oxygen affinity, and a relatively rapid oxygen dissociation rate constant. A close relative that does not fix nitrogen, Trema tomentosa, expresses hemoglobin (TremaHb) sharing 93% amino acid identity to ParaHb, but its phylogeny predicts a typical nonsymbiotic hemoglobin with a hexacoordinate heme iron, high oxygen affinity, and slow oxygen dissociation rate constant. Here we characterize heme coordination and oxygen binding in TremaHb and ParaHb to investigate whether or not two hemoglobins with such high sequence similarity are actually so different in functional behavior. Our results indicate that the two proteins resemble nonsymbiotic hemoglobins in the ferric oxidation state and symbiotic hemoglobins in the ferrous oxidation state. They differ from each other only in oxygen affinity and oxygen dissociation rate constants, two factors key to their different functions. These results demonstrate distinct mechanisms for convergent evolution of oxygen transport in different phylogenetic classes of plant hemoglobins.

Plant hemoglobins: a molecular fossil record for the evolution of oxygen transport.

The evolution of oxygen transport hemoglobins occurred on at least two independent occasions. The earliest event led to myoglobin and red blood cell hemoglobin in animals. In plants, oxygen transport "leghemoglobins" evolved much more recently. In both events, pentacoordinate heme sites capable of inert oxygen transfer evolved from hexacoordinate hemoglobins that have unrelated functions. High sequence homology between hexacoordinate and pentacoordinate hemoglobins in plants has poised them for potential structural analysis leading to a molecular understanding of this important evolutionary event. However, the lack of a plant hexacoordinate hemoglobin structure in the exogenously ligand-bound form has prevented such comparison. Here we report the crystal structure of the cyanide-bound hexacoordinate hemoglobin from barley. This presents the first opportunity to examine conformational changes in plant hexacoordinate hemoglobins upon exogenous ligand binding, and reveals structural mechanisms for stabilizing the high-energy pentacoordinate heme conformation critical to the evolution of reversible oxygen binding hemoglobins.