Validation of the first step of the heuristic refinement method for the derivation of solution structures of proteins from NMR data

A new method for the analysis of NMR data in terms of the solution structure of proteins has been developed. The method consists of two steps: first a systematic search of the conformational space to define the region allowed by the initial set of experimental constraints, and second, the narrowing of this region by the introduction of additional constraints and optional refinement procedures. The search of the conformational space is guided by heuristics to make it computationally feasible. The method is therefore called the heuristic refinement method and is coded in an expert system called PROTEAN. The paper describes the validation of the first step of the method using an artificial NMR data set generated from the known crystal structure of sperm whale carbon monoxymyoglobin. It is shown that the initial search procedure yields a low-resolution structure of the myoglobin molecule, accurately reproducing its main topological features, and that the precision of the structure depends on the quality of the initial data set.     

Ion-Exchange Chromatography Separates Activities Synthesizing and Degrading Fructose 2,6-Bisphosphate from C3 and C4 Leaves but Not from Rat Liver

Fructose-6-phosphate,2-kinase and fructose-2,6-bisphosphatase were separated on the basis of charge from leaves of C₃ (spinach, lettuce, and pea) and C₄ (sorghum and amaranthus) plants but not from rat liver—a tissue known to contain a bifunctional enzyme with both activities. [2-³²P]Fructose 2,6-bisphosphate binding experiments also suggest that the major forms of these activities reside on different proteins in leaves.     

Effect of cleft palate repair and pharyngeal flap surgery on upper airway obstruction during sleep

The effect of von Langenbeck palatoplasty and pharyngeal flap surgery on upper airway obstruction during sleep was studied by obtaining polysomnographic sleep studies on 10 patients undergoing each procedure at 1 to 2 days prior to surgery, 2 to 3 days postoperatively, and approximately 3 months postoperatively. The effects of von Langenbeck palatoplasty on sleep-related upper airway obstruction were usually minimal and clinically insignificant, whereas severe obstructive sleep apnea was present in all but one of the patients undergoing pharyngeal flap surgery at 2 to 3 days postoperatively. In most patients the upper airway obstruction was resolved at the 3-month postoperative sleep study. These data suggest that palatoplasty carries with it a very slight risk of upper airway obstruction, whereas pharyngeal flap surgery has as a very frequent concomitant the occurrence of severe obstructive sleep apnea in the immediate postoperative period.     

Immunoreactivity to the pancreatic polypeptide family in the nervous system of the adult human blood fluke,Schistosoma mansoni

Summary The presence and distribution of neuropeptides belonging to the pancreatic polypeptide family have been demonstrated by an indirect immunofluorescence technique in the nervous systems of adult male and female Schistosoma mansoni. Seven antisera of differing regional specificity to pancreatic polypeptide (PP), peptide YY (PYY) and neuropeptide Y (NPY) were employed on both whole-mount and cryostat-sectioned material. Positive immunoreactivity (IR) was obtained with all antisera except an N-terminally-directed antiserum to NPY. In the CNS, immunoreactivity was restricted to cell bodies and nerve fibres in the anterior ganglia, central commissure and dorsal and ventral nerve cords of both sexes, whereas, in the PNS, positive-IR was present in the plexuses innervating the subtegumental musculature and the oral and ventral suckers. Intense immunoreactivity was observed in a plexus of nerve fibres and cell bodies in the lining of the gynaecophoric canal and in fine nerve fibres innervating the dorsal tubercles of the male. In contrast, in the female, strong immunoreactivity was evident in nerve plexuses innervating the lining of the ovovitelline duct and in the wall of the ootype, but most notably in a cluster of cells in the region of Mehlis' gland. Results suggest that molecules with C-terminal homology to the PP-family are present in S. mansoni. These peptides would appear to be important regulatory molecules in the parasite's nervous system and may play a role in the control of egg production.     

Principal/agent theory and decision making in health care

Principal/agent theory, an economics concept that defines an agency relationship as "a contract under which one or more persons engage another person (the agent) to perform some service on their behalf which involves delegating some decision-making authority to the agent," is held to be applicable to the patient/physician relationship, in contrast to the view that this is a fiduciary relationship, not a contractual one. The distinction between fiduciary and contractual relationships is illuminated in the process of evaluating objections to the application of the principal/agent theory to the patient/physician relationship. The ability of the principal/agent theory to reveal important features of advance directives, understood as public documents rather than as confidential instructions from patient to physician, is also examined.     

Influence of Synchro-Mate-B and breed composition on estrous response and pregnancy rate in spring- and fall-bred Brahman crossbred beef cows

Estrous response, pregnancy rate, and the relationship between palpable corpora lutea (CL) and plasma progesterone concentrations were studied during the spring (n = 149) and fall (n = 146) breeding seasons using postpartum, crossbred beef cows consisting of 0-Brahman, 1 4 - Brahman , or 1 2 Brahman breeding. At the start of each breeding season, a jugular blood sample was collected for progesterone analysis; each cow was palpated for the presence of a CL and randomly alloted within breed to a non-treated control or Synchro-Mate-B (SMB) treatment. Fewer (P<0.01) fall than spring bred cows exhibited estrus within the first 21 d of breeding. Within 48 h of implant removal, 84 and 64% (spring and fall, respectively) of synchronized cows exhibited estrus. In both seasons, more SMB than control cows became pregnant by 7 d of breeding. Percentage of Brahman breeding did not influence estrous response or pregnancy rate. On the basis of 292 evaluations, palpation per rectum correctly assessed ovarian status 74% of the time. These data indicate that although season can influence response. SMB can be used effectively to synchronize Brahman crossbred cows. In addition, it was found that there is a close relationship between palpation per rectum and plasma concentrations of progesterone.     

Changes in bone mineralization pattern: a response to local stimulus in maxilla and mandible of dogs

A pilot study was carried out in order to verify the pattern of changes in mineralization of bone in the maxillas and mandibles of dogs which had a tooth extraction or luxation. Bone mineral content was determined using computerized microdensitometry. Significant changes in patterns of mineralization were found for alveolar bone, cortical bone and trabecular bone at the sites adjacent to the area of operation. These findings suggest that the three envelopes of jaw bones of the dogs are influenced by Regional activation phenomenon (RAP). These results have important implications for the design of clinical studies of periodontium. A more detailed study should elucidate the cellular mechanisms by which these changes occur.