Adaptive evolution of the MHC class III-encoded receptor RAGE in primates and murine rodents.

The receptor for advanced glycation end products is associated with a series of physiological and pathological processes. Here, we studied the evolution of this multiligand receptor in primates and murine rodents. The evolutionary analyses reveal that adaptive selection had contributed to the variation at a number of amino acid sites in both taxa. Further, the major adaptively selected sites of both taxa are located on the extracellular ligand- and intracellular adaptor-binding regions and receptor oligomerization-related surfaces. The co-occurrence of adaptive evolution on the homologue domains suggests that they could play similar roles in these taxa. In terms of advantage fitness, the adaptive changes at these sites could contribute to host defence against the potential challenges towards these interactions and relevant signalling pathways, or the specificity of these essential points.

Disruptions of the Ustilago maydis REC2 gene identify a protein domain important in directing recombinational repair of DNA.

The REC2 gene of Ustilago maydis encodes a homologue of the Escherichia coli RecA protein and was first identified in a screen for UV-sensitive mutants. The original isolate, rec2-1, was found to be deficient in repair of DNA damage, genetic recombination and meiosis. We report here that the rec2-197 allele, which was constructed by gene disruption, retains some biological activity and is partially dominant with respect to REC2. The basis for the residual activity is probably as a result of expression of a diffusible product from the rec2-197 allele that augments or interferes with REC2 functions. This product appears to be a polypeptide expressed from a remnant of the 5' end of the open reading frame that was not removed in creating the gene disruption. The mutator activity and disturbed meiosis of rec2-197 suggest that the Rec2 protein functions in a process that avoids spontaneous mutation and insures faithful meiotic chromosome segregation. A prediction based on the phenotype of rec2-197 is that Rec2 protein interacts with one or more other proteins in directing these functions. To identify interacting proteins we performed a yeast two-hybrid screen and found Rad51 as a candidate. Rec2-197 and Rad51 appear to interact to a similar degree.

Hemodynamic effects of aerobic vs resistance exercise.

Previous studies suggest that aerobic exercise lowers blood pressure (BP), while isometric exercise increases BP, at least transiently. The purpose of this study was to examine the hemodynamic effect of a 6-week training period of aerobic exercise or weight training. Twenty deconditioned healthy males ages 18-36, self-selected a training regimen. The aerobic group exercised 30 min/day, 4 times each week to achieve 60-80% maximal heart rate. The resistance group lifted weights at 65-80% maximal voluntary contraction; 3-4 sets of 8-12 repetitions; 3 day/week using large muscle groups. Hemodynamic measurements of heart rate, BP, venous capacitance, forearm blood flow, and vascular resistance were made at baseline and week 6 by plethysmography and analyzed by 2-way ANOVA. The groups showed no differences in baseline characteristics. A training effect was confirmed by a decrease in resting heart rate in the aerobic group (71.5 +/- 4.4 to 64.5 +/- 3.7, beats per minute, P = 0.004), and an increase in total work capacity in the weight lifting group (6231 vs 7508, P = 0.01). Forearm blood flow increased similarly in both groups, averaging 17% (3.5 +/- 0.2 vs 4.2 +/- 0.2 ml 100 g/min, P = 0.03), while forearm vascular resistance fell 19% (28.8 +/- 1.7 vs 24.3 +/- 1.7 mm Hg/ml/min 100 g, P = 0.08). The main differences between the groups after training was found in their response to isometric stress (1/3 maximal handgrip). The weight-lifting group had a greater increase of forearm blood flow and venous capacitance, less increase in systolic BP (SBP) and a greater fall of forearm vascular resistance, (P < 0.05) while the aerobic group had less increase in SBP and heart rate (P < 0.04) but no significant change of forearm hemodynamics. We conclude that both aerobic and repetitive weight programs have short term favorable effects on resting forearm BP and resistance. The exercise programs differ in altering the individual's physiologic response to subsequent isometric stress. However, exercise training of longer duration or greater intensity or frequency could alter these results.

Physicochemical properties, pharmacokinetics, and biodistribution of gadoteridol injection in rats and dogs.

RATIONALE AND OBJECTIVES: The physicochemical properties of gadoteridol, a macrocyclic nonionic gadolinium complex, were studied together with its pharmacokinetics and biodistribution in rats and dogs. METHODS: Studies in rats were conducted after single intravenous injections at 0.1 or 0.35 mmol/kg using 153Gd-labeled gadoteridol or with seven daily doses of 0.1 mmol/kg to examine the levels of residual gadolinium in organs. Nonradioactive biodistribution and excretion studies were performed in dogs following injection at 0.1 mmol/kg. RESULTS: After injection, the dose was rapidly cleared from rat blood and excreted such that more than 90% of the dose appeared in the urine within 4 hr of injection. At 7 and 14 days postinjection, only extremely low levels of gadolinium were observed in liver and bone; these levels were two to eight times lower than the levels reported after the injection of gadopentetate dimeglumine. CONCLUSION: The extracellular distribution and rapid urinary excretion of gadoteridol is in agreement with data obtained with other gadolinium-containing chelates used as intravascular magnetic resonance imaging contrast agents. Differences observed in the long-term retention of gadolinium between gadoteridol and gadopentetate dimeglumine were consistent with the reported greater in vivo resistance to transmetallation of gadolinium macrocycles compared with the linear gadolinium chelate molecules.

Behavioral and hormonal correlates of alternative reproductive strategies in a polygynous lizard: tests of the relative plasticity and challenge hypotheses.

Species with alternative reproductive tacts are good models to investigate the poorly understood question of whether individual variation within sexes results from the same physiological mechanisms that control variation between sexes. We have shown previously that adult male tree lizards, Urosaurus ornatus, of different throat color morphs express different levels of aggression in the laboratory. Further field results support the suggestion that the two morphs practice alternative reproductive tactics because the two morphs express different levels of aggressive behavior under field conditions and exhibit dramatic and opposite responses to aggressive challenges. However, despite these behavioral differences, the two morphs do not differ in levels of testosterone or corticosterone either in undisturbed situations or following aggressive challenge. These results are consistent with the relative plasticity hypothesis which proposes that organizational, rather than activational, actions of steroid hormones will be more important in morph differentiation when morphs are fixed in adult life, as they are in tree lizards. These results also support the hypothesis that steroid hormonal levels are insensitive to social modulation in males of species such as U. ornatus without paternal care.

Reciprocal changes in corticosterone and testosterone levels following acute and chronic handling stress in the tree lizard, Urosaurus ornatus.

To examine the reciprocal interactions among gonadal and adrenal steroid secretion, male tree lizards (Urosaurus ornatus) were subjected to two forms of stress. They were subjected either to the acute stress of being held in collecting bags for up to 4 hr or to the chronic stress of being maintained in individual cages in the laboratory for up to 3 weeks. In both cases, levels in stressed animals were compared to levels in free-living animals as controls. Under both conditions plasma levels of corticosterone increased and plasma levels of testosterone decreased compared to free-living controls. The response to the acute stress was much greater for both hormones than to the chronic stress, although in both cases testosterone levels changed less in response to stress than corticosterone levels. The corticosterone response to acute stress was extremely rapid with levels increasing over six-fold in the first 10 min. Plasma levels of corticosterone and testosterone were negatively correlated among individuals in the chronic stress experiment, but not in the acute stress experiment. This correlational evidence is consistent with the hypothesis of a direct effect of corticosterone levels on testosterone levels and suggests that these may only be expressed under some conditions.

Managing changes in clinical and administrative roles: staying on top with a union.

Organizations invite unions by poor management. The arrival of a union is a statement that significant organizational change is needed. Managing after the union comes should focus on seizing the initiative for organizational change and enlarging management control. Nonunionized agencies should evaluate their susceptibility to unionization and take preventive action.

Metabolism and kinetics of atracurium: an overview.

Atracurium, a new competitive neuromuscular blocking agent, is broken down in the body by two mechanisms, Hofmann elimination and ester hydrolysis. Chemical breakdown by Hofmann elimination is rapid at physiological pH and temperature, whereas ester hydrolysis is enzyme-catalysed but by enzymes other than pseudocholinesterase. The products of these reactions have been shown to lack neuromuscular or cardiovascular activity at the concentrations occurring after therapeutic doses of atracurium. Studies with radiolabelled drug in anaesthetized cats have shown that atracurium and its metabolites are readily excreted in bile and urine. Plasma kinetics are unaltered if renal function is negated by bilateral ligation of all renal blood vessels. Preliminary studies have indicated that atracurium does not cross the placenta to a significant extent and that the drug can be used safety in Caesarean section.

Autonomic hyperreflexia following passive stretching to the hip joint.

Autonomic hyperreflexia may occur in patients with severe upper thoracic and cervical spinal cord lesions. This syndrome, consisting of episodic hypertension, bradycardia, diaphoresis, and headaches, is an autonomic reflex evoked by a variety of stimuli applied below the level of injury. This article describes three cases in which autonomic hyperreflexia was provoked by passive hip joint stretching.

Threats to the validity of emergency medical services evaluation: a case study of mobile intensive care units.

Much of the literature concerning emergency medical services evaluation has been criticized as unconvincing. Several sources of invalidity have comprised the interpretability of these studies. When true randomized experiments cannot be accomplished, quasi-experimental research designs offer greater interpretability than the more often used pre-experimental designs. In using quasi-experimental research designs, special attention must be given to threats to internal validity. A case study describes an evaluation of mobile intensive care units. The paper describes eighteen threats to the validity of the evaluation, as well as the methods used for their control. Whether or not evaluators can control all of the threats to the validity of their studies, these threats should be identified and their potential effects assessed wherever possible.

An outcome evaluation of counseling services provided by abortion clinics.

With the reduction in need for elective abortion as a long-term goal, the effectiveness of abortion clinic counseling programs provided at the time of elective pregnancy termination is evaluated using post-abortion contraceptive behavior as a measure. Using eight, free-standing abortion clinics located in Chicago, Illinois a control group design is employed in order to examine the hypothesis that patients attending clinics which provide a structured, comprehensive birth control counseling session at the time of their abortion will show a higher use rate of effective contraceptive methods than those patients attending clinics which do not provide such information. Results support this hypothesis. The differences are particularly noticeable in the subpopulation of teenagers with no preabortion history of contraceptive use.

Bone grafts with surface decalcified allogeneic and particulate autologous bone: report of cases.

A method for mandibular bone grafting that uses a combination of SDAB and particulate autologous cancellous bone and marrow is presented. The results of this treatment in four patients are described. Two additional maxillary bone grafts that use only SDAB are also reported. Grafts that are a combination of SDAB and cancellous autologous bone and marrow are biocompatible, anatomically contoured, easily adapted at surgery, and the allogeneic component is biodegradable. They do not require elaborate internal metallic devices for structural support.

Mandibular reconstruction. Current state of the art.

At the present time several techniques of bone grafting for restoration of mandibular defects are being employed. These methods are well established by clinical trials and animal research. Other methods are in the experimental stage. Regardless of the technique utilized it remains paramount that the surgeon plan the initial procedure with great care as each failure results in diminished blood supply to the graft bed and makes subsequent procedures less likely to succeed. The well known principles of bone grafting involve establishing good nutritional status of the patient, proper preparation of the graft bed by insuring adequate soft tissue and adequate blood supply, elimination of infection from the graft bed, provision of adequate fixation and immobilization of the graft, and careful closure of soft tissues to prevent hematoma formation. These principles remain inviolable if the procedure is to succeed.