Ligand binding and covalent structure of an oxygen-binding heme protein from Rhodobacter sphaeroides, a representative of a new structural family of c-type cytochromes

The amino acid sequence of an oxygen-binding heme protein (SHP) from Rhodobacter sphaeroides has been determined. The cysteines, which bind the single heme group in the 112-residue protein, are located at positions 43 and 46. SHP is similar in size to the large membrane-bound form of the class I cytochrome c5 of Azotobacter vinelandii (116 residues) and in the location of the heme binding site at positions 48 and 51. Two extra cysteines in SHP (residues 89 and 97) are located in positions similar to those of cytochrome c5 (residues 98 and 101) and form a disulfide bridge in both proteins. In total, four regions of alpha-helix are predicted, covering 46% of the protein, which is comparable to that in other small cytochromes. SHP is thus distantly related to small class I c-type cytochromes but is representative of a distinct family by virtue of its high-spin nature, the lack of a strong sixth ligand, and its capacity to bind oxygen. Potentially, the most important characteristic of SHP is its ability to transiently bind oxygen during autoxidation, which occurs with a half-life of 3 min with a 4-fold excess of O2. SHP also binds carbon monoxide, azide, and cyanide. The kinetics of reduction by free flavins indicate that SHP is less reactive than other class I cytochromes c and that the heme is less accessible to solvent. There is localized positive charge (+3) at the site of reduction of SHP, although the overall protein charge is -2. This may account in part for the ability of SHP to bind anions.     

Comparative review of the adverse effects of sedatives used in children undergoing outpatient procedures

Children often fear medical procedures and interventions. Sedative agents enhance the care of these children who undergo outpatient procedures by decreasing anxiety, increasing cooperativity, and providing amnesia. Although higher dosages and intravenous administration of sedatives often produce improved sedation, adverse effects and complications are more frequent. The goals of therapeutic efficacy and safety must be balanced in all patients. The presence or anticipation of anxiety and pain helps in deciding whether to use a sedative alone, or a regimen also providing analgesia. The patient's clinical cardiorespiratory or neurological status, other relative contraindications, the duration of the intended procedure, and the presence or absence of an intravenous line will help in choosing specific drugs. Drug complications are a common cause of adverse events in patients. The combination of a sedative and analgesic, especially a benzodiazepine and an opioid given intravenously, is associated with a higher risk of serious complications. The practitioner responsible for the administration of a sedative to a child must be competent in its use and have the ability to detect and manage complications. Patients who are deeply sedated should be continuously monitored and observed by an individual dedicated to this task. Vital signs and oxygen saturation should be documented at frequent intervals and the patient should be appropriately monitored until discharge criteria have been met. The risk of serious complications with these agents may be reduced with vigorous monitoring and a judicious choice of dosage.     

Differential responses in anterior pituitary luteinizing hormone (LH) content and LH beta- and alpha-subunit mRNA, and plasma concentrations of LH and testosterone, in bulls treated with the LH-releasing hormone agonist deslorelin

Tooth loss diminishes oral function and quality of life, and national health targets aim to reduce population levels of tooth loss. OBJECTIVES: The purpose of this study was to determine tooth loss incidence and predictors of tooth loss among older adults in South Australia. METHODS: Data were obtained from a cohort study of a stratified random sample of community-dwelling dentate people aged 60+ years. Interviews and oral examinations were conducted among 911 individuals at baseline and among 693 of them (76.1%) 2 years later. Incidence rates and relative risks were calculated for population subgroups and multivariate logistic regression was used to construct risk prediction models. A method was developed to calculate 95% confidence intervals (95% CI) for relative risks (RR) from logistic regression models using a Taylor series approximation. RESULTS: Some 19.5% (95% CI = 15.4-23.6%) of people lost one or more teeth during the 2 years. Men, people with a recent extraction, people who brushed their teeth infrequently, smokers and people born outside Australia had significantly (P < 0.05) greater risk of tooth loss. Baseline clinical predictors of tooth loss included more missing teeth, retained roots, decayed root surfaces, periodontal pockets and periodontal recession. In a multivariate model that controlled for baseline clinical predictors, former smokers (RR = 2.55, 95% CI = 1.48-4.40) and current smokers (RR = 2.06, 95% CI = 0.92-4.62) had similarly elevated risks of tooth loss compared with non-smokers. CONCLUSIONS: The findings from this population suggest that a history of smoking contributes to tooth loss through mechanisms in addition to clinical disease processes alone.     

Effects of cigarette smoking and age on the maturation of human oocytes

We investigated whether cigarette smoking, measured by follicular fluid concentrations of cotinine (a major metabolite of nicotine), affects the maturity of oocytes from women undergoing in-vitro fertilization (IVF) and embryo transfer. In 234 women, follicular fluid samples were assessed for cotinine and their 2020 oocytes were assessed for maturity stage. Data on individual proportions of oocytes which were mature (OM) and were fertilized (OF) were analysed by regression in relation to age and follicular fluid cotinine. OF gave an independent assessment of oocyte maturity. Both age and follicular fluid cotinine entered the OM and OF regressions and were significant. The age-adjusted regression coefficients for log cotinine were positive; greater cotinine concentrations usually accompanied greater OM and OF. The cotinine effect on OM was positive in younger women, but it became negative (decreased OM with increasing cotinine concentrations) in older women (> or = 40 years). We further found in older women an average reduction of approximately 50% in the number of mature oocytes; this reduced number was lower than the number of embryos usually transferred. Smoking can reduce the number of mature oocytes even further, therefore risking a negative IVF-embryo transfer outcome. This may be the reason why the negative effects of smoking become clinically detectable in older women.     

Effects of preload, afterload and inotropy on dynamics of ischemic segmental wall motion

OBJECTIVES: This study sought to explore the separate and combined effects of changes in preload, afterload and contractility on the dynamics of systolic bulging. BACKGROUND: The extent of ischemic systolic bulging has been shown to be mechanically disadvantageous to left ventricular pump performance. The factors that determine ischemic segmental wall motion have not been systematically studied. METHODS: Fourteen beagles were instrumented with sonomicrometers, micromanometer pressure gauges and a balloon in the inferior vena cava. Regional function was evaluated before and after 90 s of proximal left circumflex coronary artery occlusion. Occlusions were repeated after increasing systolic pressure by 5 to 10 (afterload I) and 15 to 20 mm Hg (afterload II) with graded aortic occlusion during inotropic stimulation with dobutamine (2.5 and 5 micrograms/kg body weight per min intravenously), with simultaneous 5 micrograms/kg per min dobutamine infusion and afterload II and during 2.5% halothane (negative inotrope) concentration. A 20-min recovery period was allowed between each stage of the experiment so that regional function returned to its preocclusion level. Ischemic wall motion was characterized by percent systolic bulging and its peak positive systolic lengthening rate (+dL/dt). RESULTS: Because bulging is markedly influenced by regional preload, systolic bulging was characterized over a wide range of end-diastolic lengths of the ischemic segment during caval balloon occlusion. During each intervention, a decrease in regional preload increased the extent of percent systolic bulging. This preload dependency was more pronounced with dobutamine infusions. An increase in afterload was not associated with increased percent systolic bulging at any given preload. At a predetermined preload, bulging was not appreciably altered when an increase in left ventricular systolic pressure was not associated with a change in peak positive first derivative of left ventricular pressure (+dP/dt) but was significantly worse when peak +dP/dt increased. Dobutamine caused a dose-dependent increase in percent systolic bulging and peak +dL/dt that was positively correlated with peak +dP/dt. CONCLUSIONS: By using different loading and inotropic interventions and analyzing the regional wall motion behavior over a range of regional preloads, we can conclude that preload and rate of pressure (tension) development are the principal determinants of systolic bulging. Increases in left ventricular pressure alone had a minimal effect on systolic bulging.     

EEG monitoring during carotid surgery: who should do the monitoring?

Recently, a new hematopoietic growth factor, stem cell factor, the ligand for the c-kit-proto-oncogene, has been cloned. The gene for this factor or for its receptor are deleted in two well known series of mice mutants which display pleiotropic stem cell defects. Therefore, this factor supposedly plays an important role in stem cell biology. This paper reviews some of the elegant genetic work which led to the discovery of the factor and of its receptor, the biological effects that this factor exerts in the hematopoietic system in normal individuals and in patients with Diamond-Blackfan anemia and speculates on some of its potential clinical applications.     

Allelic polymorphism of the DNA-loci met and D7S23, linked to the mucoviscidosis gene in human populations of the Volga-Ural region

Data on allelic polymorphism of MET and D7S23 DNA loci linked to the human cystic fibrosis gene studied in three Bashkir ethnic groups and some Volga-Ural populations (Tartars, Maris, Mordovians, Udmurts, Chuvashs, and Komis) are presented. Udmurts were found to be substantially different from Bashkirs, Tartars, Mordovians, and Chuvashs by the allele frequency distribution observed for MET, while Komis and Bashkirs differed by this parameter from Mordovians and Maris. Comparative analysis of restriction fragment length polymorphism (RFLP) at the D7S23 locus revealed statistically significant differences in genotype frequencies between Bashkirs of the Arkhangel' skii region and populations of Mordva and Udmurtia. In this respect, the Mordovian population appeared to be notably different from the populations of Bashkortostan, Tatarstan, Marii-El, Udmurtiya, Chuvashiya, and Komis. Genetic distances were calculated and corresponding dendrograms were constructed on the basis of data on Met-H, CS.7, and the ApoB locus hypervariable region allelic frequencies. Three ethnogeographic Bashkir groups belonging to one tree branch were found to be closely related to the populations of Tartars, Maris, Udmurts, and Chuvashs and substantially different from Komis and Mordovians. Thus, the position of Volga-Ural populations on the dendrogram corresponds to the degree of relationship between the Finno-Ugric and Turkic populations, confirming the usefulness of DNA polymorphism analysis for the study of the genetic structure of populations.     

General solution of one-dimensional,time dependent coupled heat flow systems

A new, powerful method of analysis, involving the combined use of finite integral transform and finite element techniques, is presented for the solution of time dependent heat flow systems composed of many one-dimensional elements connected through the nodes. This method leads to an eigenvalue problem which is not of the conventional Sturm-Liouville type. A procedure for the determination of the eigenvalues is described. The solution obtained is in the form of an infinite series and contains quasi-steady and transient terms. The general solution obtained can be applied in the mathematical modelling of many engineering applications such as the determination of the penetration of the daily temperature cycle into buildings, the analysis of heat transfer in array of extended surfaces in compact heat exchangers, and many others.     

Receptor-associated protein (RAP): a specialized chaperone for endocytic receptors

A number of cellular control mechanisms have evolved that facilitate and evaluate post-translational steps in protein biosynthesis. Chaperones or escort proteins are an important part of these cellular control mechanisms. They associate with newly synthesized proteins and assure correct folding and post-translational modification including disulfide bridge formation, glycosylation and complex formation. The receptor-associated protein (RAP) is a novel type of chaperone recently identified that is especially designed to assist in the biosynthesis and intracellular transport of endocytic receptors. Experimental evidence suggests that RAP acts as a receptor antagonist and prevents association of newly synthesized receptors with their ligands during transport to the cell surface. This mechanism seems to be required in cell types that express both receptor and ligand because premature receptor-ligand interaction in the secretory pathway interferes with proper export of the receptors to the cell surface. This review describes studies that have uncovered this unique protein biosynthesis mechanism.