No evidence for linkage of a novel CA repeat polymorphism for apoptosis antigen 1 (APO-1 or fas) with type I diabetes in a Caucasian population

Abstract DNA typing of four tetrameric repeat loci (HUMVWA, HUMTH0I, D21SII and HPRT) was carried out in a Chinese Han population from Shanghai (East China) and one from Guangzhou (South-East China) using a quadruplex PCR amplification and detection of the fluorescent-labeled alleles on the ALF DNA sequencer. All loci were in accordance with Hardy-Weinberg equilibrium except for D21S11 in the Guangzhou population. A test for population differentiation showed no statistical difference in the allele frequency distribution between the two populations. Comparison of the allele frequency data with other Chinese Han populations from North and South-West China for the STR loci HUMVWA and HUMTH01 revealed heterogeneity between Northern Chinese Han and Southern Chinese Han, which is in accordance with previous studies on the basis of protein markers.     

Biomechanical study of sternal closure using rigid fixation techniques in human cadavers

BACKGROUND: We believe rigid plate fixation may be superior to wire fixation in sternal closure, as rigid fixation used in the craniofacial skeleton has shown greater stability, lower postoperative pain, and accelerated bone healing. We hypothesize that sterna fixed with titanium plates are more stable mechanically than sterna fixed with wires. METHODS: The sterna from human cadavers were used in this two-phased study. Phase I compared wires to four-hole titanium straight plates. Phase II compared wires to four-hole titanium custom H plates. The sterna were tested biomechanically using all fixation methods. RESULTS: Phase I showed no statistically significant difference in the stiffness or lateral displacement between the wired and straight plated sterna. Phase II showed a statistically significant greater stiffness (p < 0.05) and less lateral displacement (p < 0.05) in the custom plated sterna over the wired sterna. CONCLUSIONS: Our results showed that custom titanium H plates were superior to wire fixation. Furthermore, our results established the importance of plate configuration in sternal fixation. Our study may have beneficial clinical implications, as decreased motion at the sternotomy site could mean less postoperative pain, a decreased incidence of infection, and accelerated bone healing.     

Implication of eIF2B rather than eIF4E in the regulation of global protein synthesis by amino acids in L6 myoblasts

The present study was designed to investigate the mechanism through which leucine and histidine regulate translation initiation in L6 myoblasts. The results show that both amino acids stimulate initiation and coordinately regulate the activity of eukaryotic initiation factor eIF2B. The changes in eIF2B activity could be explained in part by modulation of the phosphorylation state of the alpha-subunit of eIF2. The activity changes might also be a result of modulation of the phosphorylation state of the eIF2B epsilon-subunit, because deprivation of either amino acid caused a decrease in eIF2Bepsilon kinase activity. Leucine, but not histidine, additionally caused a redistribution of eIF4E from the inactive eIF4E.4E-BP1 complex to the active eIF4E.eIF4G complex. The redistribution was a result of increased phosphorylation of 4E-BP1. The changes in 4E-BP1 phosphorylation and eIF4E redistribution associated with leucine deprivation were not observed in the presence of insulin. However, the leucine- and histidine-induced alterations in global protein synthesis and eIF2B activity were maintained in the presence of the hormone. Overall, the results suggest that both leucine and histidine regulate global protein synthesis through modulation of eIF2B activity. Furthermore, under the conditions employed herein, alterations in eIF4E availability are not rate-controlling for global protein synthesis but might be necessary for regulation of translation of specific mRNAs.     

Development of orally active oxytocin antagonists: studies on 1-(1-[4-[1-(2-methyl-1-oxidopyridin-3-ylmethyl)piperidin-4-yloxy]-2- methoxybenzoyl]piperidin-4-yl)-1,4-dihydrobenz[d][1,3]oxazin-2-one (L-372,662) and related pyridines

The previously reported oxytocin antagonist L-371,257 (2) has been modified at its acetylpiperidine terminus to incorporate various pyridine N-oxide groups. This modification has led to the identification of compounds with improved pharmacokinetics and excellent oral bioavailability. The pyridine N-oxide series is exemplified by L-372,662 (30), which possessed good potency in vitro (Ki = 4.1 nM, cloned human oxytocin receptor) and in vivo (intravenous AD50 = 0.71 mg/kg in the rat), excellent oral bioavailability (90% in the rat, 96% in the dog), good aqueous solubility (>8.5 mg/mL at pH 5.2) which should facilitate formulation for iv administration, and excellent selectivity against the human arginine vasopressin receptors. Incorporation of a 5-fluoro substituent on the central benzoyl ring of this class of oxytocin antagonists enhanced in vitro and in vivo potency but was detrimental to the pharmacokinetic profiles of these compounds. Although lipophilic substitution around the pyridine ring of compound 30 gave higher affinity in vitro, such substituents were a metabolic liability and caused shortfalls in vivo. Two approaches to prevent this metabolism, addition of a cyclic constraint and incorporation of trifluoromethyl groups, were examined. The former approach was ineffective because of metabolic hydroxylation on the constrained ring system, whereas the latter showed improvement in plasma pharmacokinetics in some cases.     

Assessment of regional left ventricular long-axis motion with MR velocity mapping in healthy subjects

We present a case of trichothiodystrophy associated with a hypereosinophilic syndrome. This case had been followed for 30 years. Trichothiodystrophy was characterized by lamellar ichthyosis, hair and nail dystrophies, kyphoscoliosis, congenital luxation of the hip. The hypereosinophilic syndrome was characterized by an itching urticaria-like eruption. Although the patient's general condition had remaining stable for 30 years, during the last year it worsened and the patient suddenly died. The authors discuss about the significance of this association.     

Abdominal and thoracoabdominal aortic aneurysm

Most abdominal aortic aneurysms (AAA) and thoracoabdominal aortic aneurysms (TAAA) are asymptomatic and are found on physical exam or incidentally during radiological studies for other indications. These aneurysms are repaired primarily because their risk of rupture increases geometrically as the size exceeds 5 cm. The potential morbidity of intraoperative visceral and spinal ischemia involved with TAAA repair may be reduced with various adjunctive maneuvers.     

Investigation of spectral reproducibility in direct analysis of bacteria proteins by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry

Matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (TOFMS) can be used for rapid detection of bacteria proteins in a crude mixture. It can potentially be used as a tool for bacterial identification based on the mass spectral patterns or the appearance of some characteristic mass peaks. However, there are many experimental parameters that can potentially have a strong effect on the observed mass spectra. The objective of this work is to address the mass spectral reproducibility issue. Several experimental parameters that may affect the MALDI spectra are systematically investigated. Results of spectral comparison from two laboratories with different operators and instrumentation are presented. It is demonstrated that minor variations in the sample/matrix preparation procedures for MALDI and in the experimental conditions used for bacterial protein extraction can result in a significant change in the observed spectra, though a number of peaks are conserved in the spectra obtained under different experimental conditions from the same bacterial sample. These conserved peaks may potentially be used as the biomarkers for bacterial identification. It is stressed that this type of investigation on spectral reproducibility should be carried out for different bacterial species in order to identify the mass spectral peaks that are consistently detected regardless of operator and nominal variations in sample preparation approach.     

Hysterosalpingo contrast sonography (HyCoSy) with SH U 454 (Echovist) for the assessment of tubal patency

A total of 88 Fallopian tubes from 44 patients was examined with hysterosalpingo contrast sonography (HyCoSy), hysterosalpingogram (HSG), and laparoscopic chromopertubation (LC) in order to assess their relative accuracy for measuring tubal patency. HyCoSy was done by transvaginal ultrasound and the contrast was SH U 454 (Echovist). The flow of multiple fractions of the contrast medium through each Fallopian tube was observed in real time in appropriate imaging planes by means of a transvaginal probe. Compared with laparoscopic results, we found a sensitivity of 85.2%, a specificity of 85.2%, a positive predictive value (PPV) of 71.9%, a negative predictive value (NPV) of 92.9% and concordance (HyCoSy/LC) of 85.2%, while the corresponding values for HSG were sensitivity = 85.2%, specificity = 83.6%, PPV = 69.7%, NPV = 92.7% and concordance (HSG/LC) of 84.1%. Compared with HSG results, HyCoSy obtained a co-positivity of 66.7%, a co-negativity of 81.8% and a concordance of 76.1%. In conclusion, HyCoSy with SH U 454 proved to be a reliable and safe modality for evaluating tubal patency; it is suitable as an outpatient diagnostic procedure to be used before more invasive procedures.     

Serum concentrations of soluble adhesion molecules in patients with colorectal cancer

The concentrations of the soluble adhesion molecules E-cadherin, E-selectin, intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) were investigated in 48 patients with colorectal cancer before treatment, and their relation to clinical, histological and routine laboratory parameters was examined. Data were collected on tumour stage at presentation, presence and sites of metastatic disease, tumour pathology and results of routine laboratory tests. Serum concentrations of ICAM-1 and VCAM-1 were significantly elevated in the patients with colorectal cancer in comparison with a group of healthy subjects (P < 0.00001). Levels of circulating ICAM-1 and VCAM-1 were increased both in patients with local and those with metastatic disease. Although elevated in some patients soluble E-cadherin and E-selectin concentrations were not significantly elevated compared with the control group (P = 0.71 and P = 0.052 respectively). The levels of circulating ICAM-1 were significantly correlated with those of VCAM-1 and E-selectin. A correlation was also found between the serum concentrations of E-selectin and ICAM-1 and alkaline phosphatase, total white cell count and platelet count. VCAM-1 was positively correlated with age and negatively with degree of tumour differentiation and haemoglobin concentration. The biological implications and possible clinical relevance of these findings are discussed.     

Enantioselective determination of oxprenolol and its metabolites in human urine by cyclodextrin-modified capillary zone electrophoresis

A stereospecific capillary electrophoresis assay for oxprenolol enantiomers and their basic metabolites in human urine has been developed using hydroxypropyl-beta-CD as a chiral selector in the mobile phase. The bioassay method has been validated and the detection limit from spiked urine samples is 0.2 micrograms/ml. The calibration curves are linear from 0.4 to 16 micrograms/ml. Extraction recovery ranged from 84.7 to 96.4% for all the compounds studied. The influence of various parameters on the chiral separation of oxprenolol and its basic metabolites have been investigated. Urinary excretion profiles of oxprenolol enantiomers and those of two metabolites have also been studied, following a single oral dose of racemic oxprenolol.