Malnutrition inflammation complex syndrome in maintenance haemodialysis patients

Malnutrition inflammation complex syndrome (MICS) occurs in maintenance haemodialysis (MHD) patients and is a strong predictor of morbidity and mortality in these patients. The aim of our study was to evaluate the influence of inflammation on the biochemical and anthropometrical parameters of the nutritional status in MHD patients. Our study was made on 154 patients (93 men and 61 women, mean age=54.7 yrs. and mean time on dialysis 84 months) over a period of 6 months. The indicator of inflammation, C-reactive protein (CRP), was measured monthly at the central laboratory by nephelometry. The assessment tools used to evaluate the influence of inflammation on the nutritional status in MHD patients were: serum albumin and cholesterol level, midarm circumference (MAC), midarm muscle circumference (MAMC), triceps skin fold thickness (TSF) and body mass index (BMI). Student's t-test was used for group mean comparison between men and women. Person's correlation r was used to determine the significance and the strength of associations. The CRP level was significantly greater in men than in women (12.9 vs. 7.97, p < 0.04). The CRP level showed a strong correlation only with the serum concentration of cholesterol (r=0.49, p < 0.000), and did not correlate with the serum albumin of the MHD patients. There was no correlation between the CRP level and the anthropometrical parameters of the MHD patients in our study. Two separate processes, inflammation and reduced protein intake, each separately contributed to causing a decrease in serum albumin concentration and anthropometrical measurements. The levels of acute phase proteins vary widely as opposed to the serum albumin level; for that reason, changes in the albumin catabolic rate or synthesis require a considerable time to become visible. The average value of the protein catabolic rate of the patients in our study was 1.01 g/kg/d, a value that showed adequate protein intake. These findings would suggest that clinical attention to the maintenance of adequate nutrition could blunt the effects of inflammation on both somatic and visceral protein stores.     

Cooperation between p53 and p130(Rb2) in induction of cellular senescence

To determine pathways cooperating with p53 in cellular senescence when the retinoblastoma protein (pRb)/p16INK4a pathway is defunct, we stably transfected the p16INK4a-negative C6 rat glioma cell line with a temperature-sensitive mutant p53. Activation of p53(Val-135) induces a switch in pocket protein expression from pRb and p107 to p130(Rb2) and stalls the cells in late G1, early S-phase at high levels of cyclin E. Maintenance of the arrest depends on the functions of p130(Rb2) repressing cyclin A. Inactivation of p53 in senescent cultures restores the pocket proteins to initial levels and initiates progression into S-phase, but the cells fail to resume proliferation, likely due to DNA damage becoming apparent in the arrest and activating apoptosis subsequent to the release from p53-dependent growth suppression. The data indicate that p53 can cooperate selectively with p130(Rb2) to induce cellular senescence, a pathway that may be relevant when the pRb/p16INK4a pathway is defunct.     

Imprint cytology of gastric mucosa biopsy--fast, simple and reliable method for detection of Helicobacter pylori infection

The aim of the study was to determine the value of gastric mucosa imprint cytology in the detection of Helicobacter pylori infection. A total of 182 biopsy specimens, from 182 randomly selected patients undergoing gastroscopy with gastric mucosa biopsy, were analyzed. Specimens were first submitted to slide imprinting and then formalin fixed for further routine histopathology. One-hundred and fifty-five specimens proved adequate for definitive comparison of the methods used for detection of Helicobacter pylori infection. Helicobacter pylori was detected by histopathology in 51 specimens and by cytology in 54 specimens. Agreement between the findings obtained by the two methods was recorded in 130 of 155 (83.1%) specimens. Positive cytology and negative histology findings were obtained in 14, and vice versa in 11 specimens. Gastric mucosa imprint cytology provides a useful method for the detection of Helicobacter pylori infection. The method is advantageous for being fast, simple and inexpensive. When the sample is obtained exclusively for confirmation of the presence of Helicobacter pylori infection, cytology reduces the time and cost of the procedure, at the same time providing data on morphological changes of gastric mucosa. Every finding suspect of malignant transformation of the mucosa can also be verified by histopathology because imprint manipulation causes no damage to the sample.     

Exam experience and some reactions to exam stress

The aim of this study was to assess the effects of previous exam experience on some psychophysiological reactions before, during and after repeated exams. A sample of 15 first year psychology students took part in the study. While the subjects were expecting a oral exam for the first time, their levels of exam apprehension, high activation and state anxiety were measured a day before, an hour before the exam and the following day. Furthermore, subjects' cardiac R-R intervals were continuously recorded from five minutes before the exam to five minutes after the exam. Four, out of 15 subjects, passed the exams at first sitting, while the rest of them failed and had to repeat it. These 11 students underwent the same procedure for the second time. The levels of exam apprehension, high activation and anxiety did not show any differences between the first and the second exam sittings. R-R interval parameters indicated a higher stress before and after the second exam sitting, while the stress level was more or less the same during both exams.     

Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts

The irreversible G1 arrest in senescent human diploid fibroblasts is probably caused by inactivation of the G1 cyclin-cyclin-dependent kinase (Cdk) complexes responsible for phosphorylation of the retinoblastoma protein (pRb). We show that the Cdk inhibitor p21(Sdi1,Cip1,Waf1), which accumulates progressively in aging cells, binds to and inactivates all cyclin E-Cdk2 complexes in senescent cells, whereas in young cells only p21-free Cdk2 complexes are active. Furthermore, the senescent-cell-cycle arrest occurs prior to the accumulation of the Cdk4-Cdk6 inhibitor p16(Ink4a), suggesting that p21 may be sufficient for this event. Accordingly, cyclin D1-associated phosphorylation of pRb at Ser-780 is lacking even in newly senescent fibroblasts that have a low amount of p16. Instead, the cyclin D1-Cdk4 and cyclin D1-Cdk6 complexes in these cells are associated with an increased amount of p21, suggesting that p21 may be responsible for inactivation of both cyclin E- and cyclin D1-associated kinase activity at the early stage of senescence. Moreover, even in the late stage of senescence when p16 is high, cyclin D1-Cdk4 complexes are persistent, albeit reduced by 相似文献   

Immunocytochemical study of the glucocorticoid receptor in rat liver nuclei after hyperthermic stress

The presence of glucocorticoid receptors (GR) in rat liver nuclei over a 24 h time period following hyperthermic stress at 41 degrees C was immunocytologically studied using unfixed nuclear smears. Liver nuclei in unstressed animals were found to be immunonegative for GR. However, intense GR immunopositivity followed by a subsequent gradual decrease in receptor levels was observed in the nuclei of test animals during the first 2 h after stress. This stress-related increase in the receptor nuclear level was greater than the increase seen after dexamethasone administration. These results suggest that hyperthermic stress could potentiate the hormonal stimulation of receptor nuclear translocation.     

The first structure of dipeptidyl-peptidase III provides insight into the catalytic mechanism and mode of substrate binding

Dipeptidyl-peptidases III (DPP III) are zinc-dependent enzymes that specifically cleave the first two amino acids from the N terminus of different length peptides. In mammals, DPP III is associated with important physiological functions and is a potential biomarker for certain types of cancer. Here, we present the 1.95-A crystal structure of yeast DPP III representing the prototype for the M49 family of metallopeptidases. It shows a novel fold with two domains forming a wide cleft containing the catalytic metal ion. DPP III exhibits no overall similarity to other metallopeptidases, such as thermolysin and neprilysin, but zinc coordination and catalytically important residues are structurally conserved. Substrate recognition is accomplished by a binding site for the N terminus of the peptide at an appropriate distance from the metal center and by a series of conserved arginine residues anchoring the C termini of different length substrates.     

Functional tyrosine residue in the active center of human dipeptidyl peptidase III

Abstract Human dipeptidyl peptidase III (DPP III) is a member of the metallopeptidase family M49 with an implied role in the pain-modulatory system and endogenous defense against oxidative stress. Here, we report the heterologous expression of human DPP III and the site-directed mutagenesis results which demonstrate a functional role for Tyr318 at the active site of this enzyme. The substitution of Tyr318 to Phe decreased kcat by two orders of magnitude without altering the binding affinity of substrate, or of a competitive hydroxamate inhibitor designed to interact with S1 and S2 subsites. The results indicate that the conserved tyrosine could be involved in transition state stabilization during the catalytic action of M49 peptidases.     

Synthesis and chemical behaviour of D-glucosyl esters of glutamic acid having the side-chain carboxyl group involved in the glycosidic linkage.

Simultaneous and stepwise deprotection of the fully benzylated D-glucosyl esters of 1-benzyl N-benzyloxycarbonyl- and N-tert-butyloxycarbonyl-L-glutamic acid (1 and 5, respectively) have been examined. Catalytic hydrogenation of 1 led to intramolecular aminolysis to give pyroglutamic acid and D-glucose, but similar treatment in the presence of trifluoroacetic acid afforded both anomers of 1-O-(L-gamma-glutamyl)-D-glucopyranose, which were characterized as trifluoroacetates (2alpha and 2beta) and converted into 2,3,4,6-tetra-O-acetyl-1-O-[1-methyl N-(acetyl)-L-glutam-5-oyl]-D-glucopyranose (4) which was also prepared by a definitive method. Hydrogenolysis of 5 gave both anomers of 1-O-[N-(tert-butyloxycarbonyl)-L-gamma-glutamyl]-D-glucopyranose (6), which, upon treatment with trifluoroacetic acid at - 10 degrees, afforded 2alpha and 2beta, respectively. The structure of 6beta was established by its conversion into 2,3,4,6-tetra-O-acetyl-1-O-[1-methyl N-(tert-butyloxycarbonyl)-L-glutam-5-oyl]-beta-D-glucopyranose (7beta), whereas similar treatment of 6alpha gave a mixture of 1,3,4,6-tetra-O-acetyl-2-O-[1-methyl N-(tert-butyloxycarbonyl)-L-glutam-5-oyl]-alpha-D-glucopyranose (9) and 7alpha. A 1 leads to 2 acyl migration occurred during esterification of the aglycon carboxyl group of 6alpha with diazomethane to give 2-O-[1-methyl N-(tert-butyloxycarbonyl)-L-glutam-5-oyl]-alpha-D-glucopyranose (8).