CaptiveSpray Differential Ion Mobility Spectrometry Device with Enhanced Ion Transmission and Improved Resolving Power.

A performance enhanced CaptiveSpray differential ion mobility device was designed and constructed by incorporating a circular channel and a gas flow homogenizing channel (GFHC) between the CaptiveSpray ion source and planar differential ion mobility spectrometry (DMS). The GFHC was used to reduce gas flow heterogeneity prior to the entrance of the DMS device. The optimal flared entrance greatly reduces gas flow velocity at the inlet region owing to its relatively large gas inlet interface, which assists in reducing disparities between the minimum and maximum gas velocity along the x-axis. The circular electrode was machined with channels along the x- and y-axis for the passage of auxiliary gas and was applied with a potential to focus the incoming ions from the CaptiveSpray source into the DMS channel. Using reserpine as a reference standard, substantial signal enhancement was achieved with a concomitant reduction of the peak width in the ionogram.

Use of group IIB metal ions as charge carriers for collision-induced dissociation of glycopeptide and glycan.

RATIONALE: Dissociation of biomolecules by tandem mass spectrometry (MS/MS) generates a variety of fragment ions which provide useful information for the structural characterization of biomolecules. Different fragmentation strategies result in different mass spectra for the same molecule and thus provide distinct features. Charge carriers play important roles in determining the dissociation pathways of the target precursor ions. The use of various transition metals ions as charge carriers of glycopeptide and glycan might provide additional structural information and needs to be investigated. METHODS: A 9.4 T SolariX FTICR mass spectrometer was used for collision-induced dissociation (CID) of glycopeptide and glycan. Group IIB metal ions, including Zn2+ , Cd2+ and Hg2+ , were used as charge carriers. Glycopeptide NLTK-M5 G2 and glycan G1F were used as the model systems. RESULTS: For Zn2+ - and Cd2+ -adducted species, cross-ring cleavages, glycosidic cleavages and cleavages along the peptide backbone could be obtained. There is a high degree of similarity in their CID spectra with that of Mg2+ ion-adducted glycopeptide species. For Hg2+ -adducted species, only glycosidic cleavages were observed in high abundance. The formation of doubly-charged ions (M2+ ) and a series of [f-H]+ fragments indicated unique dissociation pathways for Hg2+ -adducted glycopeptide. CONCLUSIONS: Zn2+ and Cd2+ -adducted glycopeptide species produced similar dissociation CID spectra, whereas Hg2+ -adducted species produced significantly different CID spectra. Similar CID dissociation features were also observed for Group IIB metal ions adducted glycan species. These results demonstrated that different metal ions might be used to tune the dissociation behaviors of glycopeptides and glycans.

Tandem Mass Spectrometry for Structural Characterization of Doubly-Charged N-Linked Glycopeptides.

Three dissociation methods, including collision-induced dissociation (CID), electron capture dissociation (ECD), and electronic excitation dissociation (EED), were systematically compared for structural characterization of doubly charged glycopeptide. CID produced distinctively different tandem mass spectra for glycopeptide adducted with different charge carriers. Protonated species produced mainly glycosidic cleavages in high abundance. CID of magnesiated glycopeptide formed more cross-ring cleavages, whereas doubly sodiated species produced cleavages at both glycan and peptide moieties. The effect of charge carriers on the fragmentation in ECD and EED was lower than that in CID. ECD produced mainly peptide backbone cleavages but limited cleavages at the glycan moiety, whereas EED of glycopeptide resulted in extensive fragmentation throughout the molecular ion regardless of the charge carriers. Magnesiated species gave, however, more cross-ring cleavages than other charge carriers did. These results demonstrated that EED of magnesiated species could be used as a one-step dissociation method for comprehensive structural analysis of glycopeptides.

Dissociation of Mannose-Rich Glycans Using Collision-Based and Electron-Based Ion Activation Methods.

Three dissociation methods, including collision-induced dissociation (CID), electron capture dissociation (ECD), and electronic excitation dissociation (EED), were evaluated for the dissociation of doubly charged glycans using sodium or magnesium ions as charge carriers. CID produced mainly glycosidic cleavages, although more cross-ring fragment ions could be obtained at higher intensities when magnesium ions were used as charge carriers [M + Mg]2+. The 0,2A3, 0,3A3, and 0,4A3 ions provided structural information on the 3 → 1 and 6 → 1 linkages of the mannoses. Some internal fragment ions, such as 2,4A5_Y3ß, were also produced in high abundance, thus providing additional information on the glycan structure. ECD produced limited fragments compared to other dissociation methods when either of the metal ions were used as charge carriers. Cross-ring fragments were obtained in relatively high abundance, with the charge mainly retained on the nonreducing end. EED produced extensive glycosidic and cross-ring cleavages when either metal charge carrier was used. A higher fragmentation efficiency was achieved and more structural-specific fragments were produced when Na+ was used as the charge carrier. Of the 31 possible cross-ring cleavages, including 0,2-, 0,4-, 1,5-, 2,4-, and 3,5-cleavages, 25 were found, thus providing extensive linkage information. A wide range of fragment ions could be obtained in all dissociation methods when Mg2+ was used as the charge carrier. Two specific analytical approaches were found to produce extensively structural-specific information on the glycans studied, namely CID of magnesiated glycans and EED of sodiated glycans. These two methods were selected to further analyze the larger mannose-rich glycans Man6GlcNAc2 and Man8GlcNAc2 and generated extensive structural information.

Rapid Differentiation of Asian and American Ginseng by Differential Ion Mobility Spectrometry-Tandem Mass Spectrometry Using Stepwise Modulation of Gas Modifier Concentration.

This study reports a rapid and robust method for the differentiation of Asian and American ginseng samples based on differential ion mobility spectrometry-tandem mass spectrometry (DMS-MS/MS). Groups of bioactive ginsenoside/pseudo-ginsenoside isomers, including Rf/Rg1/F11, Rb2/Rb3/Rc, and Rd/Re, in the ginseng extracts were sequentially separated using DMS with stepwise changes in the gas modifier concentration prior to MS analysis. The identities of the spatially separated ginsenoside/pseudo-ginsenoside isomers were confirmed by their characteristic compensation voltages at specific modifier loading and MS/MS product ions. As expected, Asian ginseng samples contained some Rf and an insignificant amount of F11, whereas American ginseng samples had a high level of F11 but no Rf. The origin of the whole and sliced ginseng could further be confirmed using the quantitative ratios of three sets of ginsenoside markers, namely, Rg1/Re, Rb1/Rg1, and Rb2/Rc. Based on our results, new benchmark ratios of Rg1/Re < 0.15, Rb1/Rg1 > 2.15, and Rb2/Rc < 0.26 were proposed for American ginseng (as opposed to Asian ginseng).

Synovial sarcoma of the ethmoidal sinus.

BACKGROUND: Synovial sarcoma is a high-grade, soft tissue, malignant disease associated with poor outcome. Typically, synovial sarcoma involves the extremities, with less than 10 per cent of cases occurring in the head and neck region. Synovial sarcoma of the paranasal sinuses is a rare entity. This paper presents a case of an elderly patient with synovial sarcoma of the ethmoidal sinus. CASE REPORT: An 80-year-old woman who had right epistaxis underwent nasal endoscopy and biopsy. The pathology indicated synovial sarcoma and the patient underwent endoscopic excision of the tumour. CONCLUSION: Synovial sarcoma of the ethmoidal sinus is very rare. Patients should undergo excision of the tumour with post-operative radiotherapy. However, the prognosis remains poor and usually the patient succumbs to death within a year.

Comparison of Visante and slit-lamp anterior segment optical coherence tomography in imaging the anterior chamber angle.

AIMS: To compare the diagnostic performance of two anterior segment optical coherence tomography (AS-OCT) devices in assessing the anterior chamber angle (ACA). METHODS: Visante-OCT and slit-lamp-OCT (SL-OCT) were performed on 101 patients by a single operator. The AS-OCT images were processed by customised 'dewarping' software and assessed by two glaucoma specialists masked to clinical findings. A closed ACA was defined by the presence of contact between the iris and angle anterior to the scleral spur. Measurements of the ACA, anterior chamber depth (ACD), and pupil diameter were analysed. Gonioscopy was performed by another examiner masked to AS-OCT findings. RESULTS: Qualitative analysis could be carried out in 83 (83%) eyes and quantitative analysis in 61 (60%) eyes. A closed angle in at least one quadrant of the eye was observed in 30 eyes with gonioscopy; Visante-OCT imaging identified 29 of 30 (97%) and SL-OCT imaging identified 27 of 30 (90%) of these eyes (P=0.50, McNemar test). Visante-OCT detected more eyes with at least one closed quadrant than SL-OCT (55 vs46 eyes, respectively, P=0.01). Overall, SL-OCT had better agreement with gonioscopy than with Visante-OCT. Both AS-OCTs showed good agreement for ACD measurements; however, SL-OCT tended to provide consistently higher ACA measurements and smaller pupil diameters than did Visante-OCT. CONCLUSIONS: Both AS-OCT devices detected most of the eyes with closed ACA on gonioscopy. However, Visante-OCT detected more closed ACAs than did SL-OCT. The better agreement between SL-OCT and gonioscopy is likely because of the use of visible light during both examinations. The ACA measurements obtained with each device are not interchangeable.

Time trends in peptic ulcer, erosive reflux oesophagitis, gastric and oesophageal cancers in a multiracial Asian population.

BACKGROUND: Dramatic changes in the prevalence and pattern of gastrointestinal disease has taken place in Asia in recent years. AIM: To compare the prevalence of duodenal (DU) and gastric ulcers (GU), erosive oesophagitis (EO), gastric cancer (GCA) and oesophageal cancer (OCA) and Helicobacter pylori infection over a 10-year interval of time in a multiracial South-East Asian population. METHODS: Endoscopy records of first time gastroscopy in the University of Malaya Medical Centre, Kuala Lumpur, Malaysia were reviewed for 1989/1990 and 1999/2000. RESULTS: In the period of 1989-1990, 3252 records and in 1999-2000, 4615 records were analysed. Both DU (21.1-9.5%) and GU (11.9-9.4%) had decreased significantly (P < 0.001). EO had increased significantly from 2.0% to 8.4% (P < 0.001). Both GCA and OCA had declined in the 10-year interval. Helicobacter pylori prevalence had decreased from 51.7% to 30.3% (P < 0.001).The decrease in DU and GU was seen in all racial groups. The increase in EO was most marked in Indians and the decrease in GCA in Chinese. The proportion of H. pylori-associated DU and GU had also decreased with time. CONCLUSIONS: Peptic ulcers and H. pylori infection had declined over a 10-year period of time and showed an opposing time trend with EO, which had increased dramatically. Both GCA and OCA had declined in prevalence.

Randomised controlled trial comparing the effect of brimonidine and timolol on visual field loss after acute primary angle closure.

AIM: To compare the effect of brimonidine and timolol in reducing visual field loss in patients with acute primary angle closure (APAC). METHODS: In addition to standard acute medical treatment, patients presenting with APAC were randomised to either brimonidine 0.2% or timolol 0.5% upon diagnosis, then twice daily for 4 weeks. After laser peripheral iridotomy (LPI), subjects underwent three baseline perimetry tests during the first week, and then at weeks 4, 8, 12, and 16. Pointwise linear regression analysis was applied to the field series of each of these subjects starting with the third test (total of five tests per subject). Progression was defined as a significant regression slope (p<0.05) showing 1 dB per year or more of sensitivity loss at the same test location in the series. Patients were also compared for prevalence of abnormal fields at 16 weeks, which was defined as an abnormal glaucoma hemifield test result and/or corrected pattern standard deviation outside the 95% confidence limits. RESULTS: 59 subjects (31 in the brimonidine group; 28 in the timolol group) completed the study. There were 47 females (79.7%), the majority of subjects (94.9%) were Chinese and the mean age was 59.2 (SD 7.2) years. There were no significant differences between the two groups with respect to demographic features, presenting intraocular pressure (IOP), duration of symptoms, time from presentation to LPI, or mean IOP at each study visit. Over the 16 week study period, despite adequate statistical power, no difference was found between groups in terms of the number of patients with progressing locations, the mean number of progressing locations per subject, or the mean slope of the progressing locations. Nine (29%) subjects in the brimonidine group and 10 (35.7%) in the timolol group were found to have significant visual field defects at 16 weeks (p = 0.58). 15 out of these 19 subjects (78.9%) already had these visual field defects in the first week. CONCLUSIONS: In the first 16 weeks after APAC, there was no difference in the prevalence of visual field defects or rate of visual field progression between brimonidine and timolol treated groups.