Medical Library

Rethinking Proteasome Evolution: Two Novel Bacterial Proteasomes.

The proteasome is a multisubunit structure that degrades proteins. Protein degradation is an essential component of regulation because proteins can become misfolded, damaged, or unnecessary. Proteasomes and their homologues vary greatly in complexity: from HslV (heat shock locus v), which is encoded by 1 gene in bacteria, to the eukaryotic 20S proteasome, which is encoded by more than 14 genes. Despite this variation in complexity, all the proteasomes are composed of homologous subunits. We searched 238 complete bacterial genomes for structures related to the proteasome and found evidence of two novel groups of bacterial proteasomes. The first, which we name Anbu, is sparsely distributed among cyanobacteria and proteobacteria. We hypothesize that Anbu must be very ancient because of its distribution within the cyanobacteria, and that it has been lost in many more recent species. We also present evidence for a fourth type of bacterial proteasome found in a few beta-proteobacteria, which we call beta-proteobacteria proteasome homologue (BPH). Sequence and structural analyses show that Anbu and BPH are both distinct from known bacterial proteasomes but have homologous structures. Anbu is encoded by one gene, so we postulate a duplication of Anbu created the 20S proteasome. Anbu\’s function appears to be related to transglutaminase activity, not the general stress response associated with HslV. We have found different combinations of Anbu, BPH, and HslV within these bacterial genomes, which raises questions about specialized protein degradation systems.

Valas RE, Bourne PE.

Bioinformatics Program, University of California, San Diego, 9500 Gilman Drive, MC 0743, La Jolla, CA, 92093, USA, rvalas@ucsd.edu.

[In Process Citation]

[Analgesic intolerance (AI) : Key position of ENT physicians for early detection of this condition.]

The clinical manifestation of analgesic intolerance (AI) is frequently associated with symptoms examined by ear-nose-throat (ENT) specialists. The prevalence of AI is reported in the literature to be 0.6-2.5%. Even though there are no concluding results concerning its pathogenesis, an altered arachidonic acid metabolism is most likely the underlying pathomechanism. The symptoms include chronic rhinosinusitis with nasal polyps, asthma, gastrointestinal ulcers, angioedema, and urticaria. Clinical reactions after ingestion of nonsteroidal anti-inflammatory-drugs (NSAIDs) are often obvious in the progress of disease. In order to initiate early therapy and therefore prevent the progress of disease, the diagnosis of AI should occur before the complete picture of AI is obvious. Adaptive desensitization is currently the single causal therapy. Frequency of endonasal revision surgery is reduced after desensitization; severe asthma and reactions after ingestion of NSAIDs are avoided. ENT specialists are particularly in a key position for early detection of AI.

Förster U, Olze H.

Klinik für Hals-Nasen-Ohren-Heilkunde, Charité-Universitätsmedizin Berlin, Campus Virchow-Klinikum, Augustenburger Platz 1, 13353, Berlin, Deutschland, ul.foerster@web.de.

Individualized growth assessment of fetal thigh circumference using three-dimensional ultrasonography.

OBJECTIVES: To develop individualized growth assessment (IGA) standards for upper (ThC(u)) and middle (ThC(m)) fetal thigh circumferences using three-dimensional ultrasonography. METHODS: A prospective, longitudinal sonographic study of 30 fetuses was performed beginning at 18 weeks’ menstrual age. Second-trimester sonographic parameters were measured from three-dimensional volume data to establish IGA standards. Normal infant growth outcomes were confirmed using modified Neonatal Growth Assessment Scores (m(3)NGAS(51)). ThC(u) and ThC(m) were studied in more detail. Rossavik growth model specification procedures, based on the slopes of the second-trimester growth curves, were developed for both ThC(u) and ThC(m). Third-trimester growth trajectories and birth measurements were subsequently predicted for these parameters. Percentage deviations during the third trimester and percentage differences at actual birth age were used to compare observed and predicted measurements. The 95% ranges for Growth Potential Realization Index (GPRI) values for both types of thigh circumference were determined. Values for m(3)NGAS(51) using GPRI(ThC(u)), GPRI(ThC(m)) and GPRI(ThC(o)) (original method) were compared. RESULTS: The 30 newborns had no postnatal evidence of abnormal growth. Two examiners demonstrated a satisfactory measurement bias of mean +/- SD 2.1 +/- 3.6 (95% limits of agreement,-4.9 to 9.1)% for ThC(m) and 3.3 +/- 4.1 (95% limits of agreement,-4.8 to 11.4)% for ThC(u). Rossavik functions fitted parameter trajectories well, with mean R(2) values of 99.5 +/- 0.4% for ThC(u) and 99.6 +/- 0.3% for ThC(m). By fixing coefficients k at their mean values, their respective fits did not change, and the variabilities of coefficients c and s were significantly reduced. For ThC(u), coefficient c was significantly related to the second-trimester slope (R(2)=98.6%), as was s to c(R(2)=91.0%). For ThC(m), coefficient c was significantly related to the second-trimester slope (R(2)=98.6%), as was s to c(R(2)=85.6%). Third-trimester growth trajectories, derived from second-trimester slopes for individual fetuses, had third-trimester deviations of 0.07 +/- 3.7% for ThC(u) and-0.04 +/- 3.7% for ThC(m). Percentage differences at birth age were 16.8 +/- 10.2% for ThC(u) and 8.9 +/- 9.5% for ThC(m). With correction for systematic overestimations, the mean GPRI values were 103.7 (95% range, 90-121)% for ThC(u) and 101.6 (95% range, 88-118)% for ThC(m). Corresponding mean +/- SD m(3)NGAS(51) values, using GPRI(ThC(u)), GPRI(ThC(m)) and GPRI(ThC(o)), were 203 +/- 11%, 201 +/- 10% and 200 +/- 9%, respectively. CONCLUSIONS: Fetal thigh circumference can be measured reliably and evaluated using standard IGA methods. Both ThC(u) and ThC(m) give similar results in the third trimester but neonatal thigh circumference predictions are improved by using ThC(m). Corresponding GPRI(ThC(m)) values are closer to the ideal value of 100% and can be used in m(3)NGAS(51) calculations for assessment of neonatal growth outcome. Copyright (c) 2008 ISUOG. Published by John Wiley & Sons, Ltd.

Ultrasound Obstet Gynecol. 2008 Apr 3
Lee W, Deter RL, Sameera S, Espinoza J, Gonçalves LF, Romero R.
Division of Fetal Imaging, Department of Obstetrics and Gynecology, William Beaumont Hospital, Royal Oak, USA.

Theoretical Study on the Complexes of Benzene with Isoelectronic Nitrogen-Containing Heterocycles

The pi-pi interactions between benzene and the aromatic nitrogen heterocycles pyridine, pyrimidine, 1,3,5-triazine, 1,2,3-triazine, 1,2,4,5-tetrazine, and 1,2,3,4,5-pentazine are systematically investigated. The T-shaped structures of all complexes studied exhibit a contraction of the C–H bond accompanied by a rather large blue shift (40-52 cm(-1)) of its stretching frequency, and they are almost isoenergetic with the corresponding displaced-parallel structures at reliable levels of theory. With increasing number of nitrogen atoms in the heterocycle, the geometries, frequencies, energies, percentage of s character at C, and the electron density in the C–H sigma antibonding orbital of the complexes all increase or decrease systematically. Decomposition analysis of the total binding energy showed that for all the complexes, the dispersion energy is the dominant attractive contribution, and a rather large attraction originating from electrostatic contribution is compensated by its exchange counterpart.

.Wang W, Hobza P.
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic and Centre for Biomolecules and Complex Molecular Systems, Flemingovo nám. 2, 166 10 Prague 6, Czech Republic, Fax: (+420)?220-410-320.
Chemphyschem. 2008 Apr 3

Investigation of the excluded stomach after Roux-en-Y gastric bypass: The role of percutaneous endoscopy.

Accessing the bypassed portion of the stomach via conventional endoscopy is difficult following Roux-en-Y gastric bypass surgery. However, endoscopic examination of the stomach and small bowel is possible through percutaneous access into the bypassed stomach (BS) with a combined radiologic and endoscopic technique. We present a case of obscure overt gastrointestinal (GI) bleeding where the source of bleeding was thought to be from the BS. After conventional endoscopic methods failed to examine the BS, percutaneous endoscopy (PE) was used as an alternative to surgical exploration.

Gill KR, McKinney JM, Stark ME, Bouras EP.

Department of Gastroenterology and Hepatology, Mayo Clinic, 4500 San Pablo Rd, Jacksonville, Florida 32224, United States. bouras.ernest@mayo.edu.

Comparison of esomeprazole enteric-coated capsules vs esomeprazole magnesium in the treatment of active duodenal ulcer: A randomized, double-blind, controlled study.

AIM: To evaluate the efficacy and tolerability of two different preparations of esomeprazole in healing duodenal ulcers. METHODS: A total of 60 patients with active duodenal ulcers were enrolled and randomized to receive esomeprazole enteric-coated capsules (40 mg) or esomeprazole magnesium (40 mg), once daily, for 4 consecutive wk, with ulcer healing being monitored by endoscopy. Safety and tolerability were also assessed. RESULTS: Fifty seven patients completed the whole trial. The ulcer healing rates at the end of wk 2 were 86.7% and 85.2% in the esomeprazole enteric-coated capsules and esomeprazole magnesium groups, respectively (P = 0.8410), and reached 100% at the end of wk 4 in both groups. Symptom relief at the end of wk 2 was 90.8% in the esomeprazole enteric-coated capsules group and 86.7% in the esomeprazole magnesium group (P = 0.5406); at the end of wk 4 symptom relief was 95.2% and 93.2%, respectively (P = 0.5786). Adverse events occurred in 16.7% of the esomeprazole enteric-coated capsules group and 14.8% of the esomeprazole magnesium group (P = 1.0000). CONCLUSION: The efficacies of esomeprazole enteric-coated capsules and esomeprazole magnesium in healing duodenal ulcer lesions and relieving gastrointestinal symptoms are equivalent. The tolerability and safety of both drugs were comparable.

Liang XY, Gao Q, Gong NP, Tang LP, Wang PL, Tao XH.

Department of Gastroenterology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China. lxyan925@yahoo.com.cn.

Double-balloon enteroscopy reliably directs surgical intervention for patients with small intestinal bleeding.

AIM: To evaluate preoperative double-balloon enteroscopy for determining bleeding lesions of small intestine, thus directing selective surgical intervention. METHODS: We retrospectively reviewed 56 patients who underwent double-balloon enteroscopy to localize intestinal bleeding prior to surgical intervention, and compared enteroscopic findings with those of intraoperation to determine the accuracy of enteroscopy in identifying and localizing the sites of small intestinal bleeding. RESULTS: Double-balloon enteroscopy was performed in all 56 patients in a 30-mo period. A possible site of blood loss was identified in 54 (96%) patients. Enteroscopy provided accurate localization of the bleeding in 53 (95%) of 56 patients, but failed to disclose the cause of bleeding in 4 (7%). There was one case with negative intraoperative finding (2%). Resection of the affected bowel was carried out except one patient who experienced rebleeding after operation. Gastrointestinal stromal tumor (GIST) was most frequently diagnosed (55%). CONCLUSION: Double-balloon enteroscopy is a safe, reliable modality for determining bleeding lesion of small intestine. This technique can be used to direct selective surgical intervention.

Lin MB, Yin L, Li JW, Hu WG, Qian QJ.

Department of Surgery, Ruijin Hospital, 197 Ruijin Er Lu, Shanghai 200025, China. lmbin@hotmail.com.

Prognostic significance of S100A4 and vascular endothelial growth factor expression in pancreatic cancer.

AIM: To investigate the expression of vascular endothelial growth factor (VEGF) and calcium-binding protein S100A4 in pancreatic cancer and their relationship to the clinicopathological parameters and prognosis of pancreatic cancer. METHODS: Expression status of VEGF and S100A4 was examined in 62 surgical specimens of primary pancreatic cancer by immunohistochemistry. Correlation between the expression of VEGF and S100A4 and clinicopathological parameters was analyzed. RESULTS: Thirty-eight of 62 (61.3%) specimens of primary pancreatic cancer were positive for S100A4. Thirty-seven (59.7%) specimens showed positive expression of VEGF. The positive correlation between S100A4 and VEGF expression was significant in cancer tissues (P < 0.001). S100A4 expression was significantly correlated with tumor size, TNM stage and poorer prognosis. VEGF expression had a significant correlation with poorer prognosis. The prognosis of 17 S100A4- and VEGF-negative cancer patients was significantly better than that of other patients (P < 0.05). Distant metastasis (P = 0.001), S100A4- (P = 0.008) and VEGF-positive expression (P = 0.016) were significantly independent prognostic predictors (P < 0.05). CONCLUSION: Over-expression of S100A4 and VEGF plays an important role in the development of pancreatic cancer. Combined examination of the two molecules might be useful in evaluating the outcome of patients with pancreatic cancer.

Ai KX, Lu LY, Huang XY, Chen W, Zhang HZ.

Department of General Surgery, 6th Affiliated Hospital of Shanghai Jiaotong University, Shanghai 200233, China. akxing8258@sina.com.

Comparative analysis of common CFTR polymorphisms poly-T, TG-repeats and M470V in a healthy Chinese population.

AIM: To investigate the three important cystic fibrosis transmembrane conductance regulator (CFTR) haplotypes poly-T, TG-repeats and the M470V polymorphisms in the Chinese population, and to compare their distribution with that in Caucasians and other Asian populations. METHODS: Genomic DNA was extracted from blood leukocytes. Exons 9 and 10 of the CFTR gene were obtained through polymerase chain reaction (PCR). Exon 9 DNA sequences were directly detected by an automated sequencer and poly-T and TG-repeats were identified by direct sequence analysis. Pure exon 10 PCR-amplified products were digested by HphI restriction enzyme and the M470V mutation was detected by the AGE photos of digestion products. RESULTS: T7 was the most common (93.6%) haplotype and the (TG)11 frequency of 57.2% and (TG)12 frequency of 40.9% were dominant haplotypes in the junction of intron 8 (IVS-8) and exon 9. The frequency of T5 was 3.8% and all T5 allele tracts (10 alleles) were joined with (TG)12. Four new alleles of T6 (1.5%) were found in three healthy individuals. In exon 10, the V allele (56.1%) was slightly more frequent than the M allele (43.9%), and the M/V (45.5%) was the dominant genotype in these individuals. The three major haplotypes T7-(TG)11-V470, T7-(TG)12-M470 and T7-TG11-M470 were related to nearly 86.0% of the population. CONCLUSION: The polymorphisms of poly-T, TG-repeats, and M470V distribution were similar to those in other East Asians, but they had marked differences in frequency from those single haplotype polymorphisms or linkage haplotypes in Caucasians. Thus, they may be able to explain the low incidence of CF and CF-like diseases in Asians.

Huang Q, Ding W, Wei MX.

Department of Traditional Chinese Medicine, the First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, Jiangsu Province, China. weimuxin@njmu.edu.cn.