Dual origins of Finns revealed by Y chromosome haplotype variation

The objective of this study was to determine effects of photoperiod and age on the circulating concentrations of LH, testosterone (T), thyroxine (T4), and semen production in male turkeys. Male turkeys from 10 or 12 wk of age were maintained under either a long-day (LD) photoperiod of 16L:8D up to 35 wk (LL), or a short-day (SD) photoperiod of 6L:18D to 29 wk and then an LD photoperiod of 16L:8D up to 35 wk of age (SL). Plasma concentrations of both LH and T increased by 17 or 18 wk of age under both photoperiods, but higher levels were attained in the LL group prior to 29 wk of age. Both LH and T levels increased significantly within days in the SL group after the group was switched to LD at 29 wk of age. Higher levels of T4 were present in the LL group prior to sexual maturation. No differences were observed in T4 concentration between lighting treatments after sexual maturation. The LL group first produced semen at 20-22 wk of age, which was about 1 wk earlier than first semen production in the SL group. A significantly larger volume of semen was produced in the LL group at most ages. No further increase in semen production was observed in the first 6 wk after the SL group was switched to the LD photoperiod at 29 wk of age. Pulsatile patterns of LH and T were characterized by serial blood sampling at 13, 23, and 35 wk of age under both the LL and SL photoperiods. The baseline levels of both LH and T in male turkeys were influenced by age and photoperiod. However, pulse characteristics (numbers, duration, and amplitude) of LH did not change with age or lighting treatment, while pulse characteristics of T did change with age. We conclude that exposing male turkeys to an LD photoperiod from 10 or 12 wk of age advanced the age of sexual maturation and induced earlier increased concentrations of LH and T.     

Effects of postural change on aspiration in head and neck surgical patients

This study was designed to define the effects of postural change on liquid aspiration during videofluorographic examination of oropharyngeal swallow in head and neck surgical patients. Thirty-two patients were given two swallows of five different amounts of liquid barium as tolerated. When aspiration occurred, the patient's head and/or body position was changed, new posture being determined by the swallowing disorder identified as the cause of the aspiration. Postural techniques were successful in eliminating aspiration on at least one volume of liquid in 81% of these patients. Patients in all surgical groups were able to use postures with equal success. A variety of positions were used in each type of surgical patient, indicating that these patients exhibited a variety of swallowing problems. Results emphasize the importance of introducing postural techniques during the radiographic study of oropharyngeal swallow to facilitate safe oral intake of liquids.     

Single-cell measurements of human neutrophil activation using electrorotation

We have used the technique of cell electrorotation within a microfabricated planar gold electrode array as a means of detecting changes in the physical properties of a single human neutrophil, when activated by the chemotactic factor, phorbol myristate acetate (PMA). The results, which have been analyzed using a double-shell model to represent the cell and its nucleus, provide an indication of the changes in biophysical parameters that occur during cell activation. The methods used in this study have potential applications in the development of single-cell assays for pharmaceutical screening, as a means of determining rapidly the action of drugs.     

Immunization of Aotus monkeys with recombinant Plasmodium falciparum hybrid proteins does not reproducibly result in protection from malaria infection

Plasmodium falciparum antigens SERP, HRPII, MSAI, and 41-3 have shown promise as vaccine components. This study aimed at reproducing and extending previous results using three hybrid molecules. Antibody responses were reproduced in Aotus monkeys, but solid protection from a P. falciparum blood-stage challenge that showed an unintendedly enhanced pathogenicity was not observed.     

Evolution of malaria in Africa for the past 40 years: impact of climatic and human factors

MOTIVATION: Prediction methods for identifying binding peptides could minimize the number of peptides required to be synthesized and assayed, and thereby facilitate the identification of potential T-cell epitopes. We developed a bioinformatic method for the prediction of peptide binding to MHC class II molecules. RESULTS: Experimental binding data and expert knowledge of anchor positions and binding motifs were combined with an evolutionary algorithm (EA) and an artificial neural network (ANN): binding data extraction --> peptide alignment --> ANN training and classification . This method, termed PERUN, was implemented for the prediction of peptides that bind to HLA-DR4(B1*0401). The respective positive predictive values of PERUN predictions of high-, moderate-, low- and zero-affinity binders were assessed as 0.8, 0.7, 0.5 and 0.8 by cross-validation, and 1.0, 0.8, 0.3 and 0.7 by experimental binding. This illustrates the synergy between experimentation and computer modeling, and its application to the identification of potential immunotherapeutic peptides. AVAILABILITY: Software and data are available from the authors upon request. CONTACT: vladimir@wehi.edu. au     

Violent emergence from anesthesia: is it a pharmacological or psychological reaction?

A violent emergence from deep sedation is an uncommon reaction in the daily practice of anesthesia in the oral and maxillofacial surgery office. We present a case of a 22-yr-old male with a severe violent emergence from deep sedation that we attribute to a psychological rather than a pharmacological cause. A differential diagnosis is discussed, as are methods of treatment.     

Propagation of mechanically induced intercellular calcium waves via gap junctions and ATP receptors in rat liver epithelial cells

Mechanical stimulation was used to initiate Ca2+ waves in rat liver epithelial cells in order to ascertain the degree to which gap junctional intercellular communication (GJIC) is involved in communication of Ca2+ to adjacent cells and to assess alternative Ca2+ signaling pathways that may be present between these cells. In both WB-F344 cells, which show a high degree of GJIC, and WB-aB1 cells, which are GJIC deficient, mechanical stimulation of a single cell induced a Ca2+ wave which propagated away from the point of stimulation, across cell borders, to neighboring cells directly or indirectly in contact with the stimulated cell. In addition, the Ca2+ wave was transmitted to nearby isolated cells that exhibited no direct or indirect contact with the stimulated cell. Treatment of cells with 18beta-glycyrrhetinic acid, a compound that has been shown to block GJIC, did not significantly affect propagation of the Ca2+ wave. In contrast, treatment with suramin, a P2-purinergic receptor inhibitor, significantly reduced both the rate and the extent of Ca2+ wave propagation in WB-F344 cells and completely blocked its propagation in WB-aB1 cells. Cotreatment with suramin and glycyrrhetinic acid was found to completely block the mechanically induced Ca2+ wave in both cell lines. These studies indicate that mechanically induced cell injury in rat liver epithelial cells initiates signaling through at least two pathways, involving intercellular communication via gap junctions and extracellular communication via ATP activation of purinergic receptors.     

Improved biochemical variables, nutrient intake, and hormonal factors in slow nocturnal hemodialysis: a pilot study

OBJECTIVE: To determine whether slow nocturnal hemodialysis (SNHD) can be safely performed in patients with end-stage renal disease to improve the biochemical and clinical outcome. MATERIAL AND METHODS: We conducted an 8-week pilot study in nondiabetic adult patients, who underwent dialysis 6 nights per week for 8 hours each night. A dialysate flow rate of 300 mL/min and a blood flow rate of 250 mL/min, through an internal jugular dual-lumen venous catheter, were used. The equipment used was a COBE Centry System 3 dialysis machine and Fresenius F-80 (1.8 m2) or Baxter CT 190 (1.9 m2) dialyzers. Five patients were enrolled in the study. RESULTS: Two patients did not complete the study because of catheter-related infections--one at day 7 and one after 4 weeks of SNHD. All patients had improved blood pressure control, and no intradialytic adverse events occurred. Dietary intake improved, urea and creatinine levels significantly decreased, and weekly delivery of dialysate increased on SNHD. Potassium, chloride, beta 2-microglobulin, phosphorus, calcium, and high-density lipoprotein cholesterol all improved on SNHD. Serum testosterone increased in the three men on SNHD, but parathyroid hormone, luteinizing hormone, and follicle-stimulating hormone remained unchanged. Erythropoietin levels increased on SNHD, despite no change in exogenous erythropoietin doses in three patients and discontinuation of administration of erythropoietin in one. The following biochemical factors did not change significantly: serum sodium, bicarbonate, vitamin B12, folate, alkaline phosphatase, total cholesterol, triglycerides, and albumin. CONCLUSION: Higher doses of hemodialysis benefit nutrition, improve biochemical variables, and may improve many hormonal systems.     

Competition between folding and glycosylation in the endoplasmic reticulum

Using carboxypeptidase Y in Saccharomyces cerevisiae as a model system, the in vivo relationship between protein folding and N-glycosylation was studied. Seven new sites for N-glycosylation were introduced at positions buried in the folded protein structure. The level of glycosylation of such new acceptor sites was analysed by pulse-labelling under two sets of conditions that are known to reduce the rate of folding: (i) addition of dithiothreitol to the growth medium and (ii) introduction of deletions in the propeptide. A variety of effects was observed, depending on the position of the new acceptor sites. In some cases, all the newly synthesized mutant protein was modified at the novel site while in others no modification took place. In the most interesting category of mutants, the level of glycosylation was dependent on the conditions for folding. This shows that folding and glycosylation reactions can compete in vivo and that glycosylation does not necessarily precede folding. The approach described may be generally applicable for the analysis of protein folding in vivo.