Imaging mass spectrometry statistical analysis

Imaging mass spectrometry is increasingly used to identify new candidate biomarkers. This clinical application of imaging mass spectrometry is highly multidisciplinary: expertise in mass spectrometry is necessary to acquire high quality data, histology is required to accurately label the origin of each pixel's mass spectrum, disease biology is necessary to understand the potential meaning of the imaging mass spectrometry results, and statistics to assess the confidence of any findings. Imaging mass spectrometry data analysis is further complicated because of the unique nature of the data (within the mass spectrometry field); several of the assumptions implicit in the analysis of LC-MS/profiling datasets are not applicable to imaging. The very large size of imaging datasets and the reporting of many data analysis routines, combined with inadequate training and accessible reviews, have exacerbated this problem. In this paper we provide an accessible review of the nature of imaging data and the different strategies by which the data may be analyzed. Particular attention is paid to the assumptions of the data analysis routines to ensure that the reader is apprised of their correct usage in imaging mass spectrometry research.     

Subcellular degeneration of mycetomal endocytobionts in tsetse,Glossina morsitans morsitans,inoculated twice withEscherichia coli

Specimens of mycetome, a portion of anterior midgut harboring intracellular bacterioids (endocytobionts), obtained from both untreated control female tsetse,Glossina morsitans morsitans, and those inoculated twice with strain D31 ofEscherichia coli, were processed for routine electron microscopy, and the endocytobionts were examined for structural alterations. In the controls, mycetocytes contained intact bacterioids with numerous, electron-dense ribosomal particles in the cytoplasm. FemaleG. m. morsitans subjected to two hemocoelic inoculations with the liveE. coli showed severe degeneration of the subcellular components of the endocytobionts characterized by advanced lysis and rarefaction. The observed endocytobiotic degeneration is attributed to effects of induced humoral antibacterial factors.     

Erythrocyte metabolism in two species of bats: common bent-wing bat (Miniopterus schreibersii) and red fruit bat (Pteropus scapulatus).

1. Metabolic intermediates, substrate utilization and enzyme activities were determined in the red blood cells of the common bent-wing bat and the red fruit bat. Standard haematological parameters and oxy-haemoglobin dissociation curves were also determined in both species. 2. The glycolytic rate as measured by lactate production was much higher for all substrates in the bent-wing bats. The activities of the glycolytic enzymes were also much higher in this species. 3. The standard haematological parameters were similar for the two species. The levels of 2,3-diphosphoglycerate (DPG) in the red cells of the fruit bat were nearly twice as high as those in the bent-wing bats. 4. The oxy-haemoglobin dissociation curve for the red fruit bat was located to the right of that for the bent-wing bat and both these curves were located to the right of that normally seen for human blood. 5. Both species of bat show blood characteristics well adapted to carrying the increased oxygen demands of flight.     

Prevalence of cervical pathogens in women with and without inflammatory changes on smear testing.

OBJECTIVE--To assess correlation between nonspecific cervicitis, inflammation, or exudate on cervical smears tests and confirmed presence of known cervical pathogens. DESIGN--Investigation of women attending a family practice clinic for smear test by microbiological screening for Chlamydia trachomatis, Mycoplasma hominis, Ureaplasma urealyticum, Trichomonas vaginalis, Candida species, group B streptococcus, Gardnerella vaginalis, and Neisseria gonorrhoeae. SETTING--Family practice teaching clinic in a university hospital. PATIENTS--411 women presenting for a smear test. MAIN OUTCOME MEASURES--Prevalence of genital infections associated with presence or absence of inflammatory changes on cervical smear. RESULTS--Of the 132 women with inflammatory changes on cervical smear, 64 (48%) had positive cultures. Of the 248 without inflammatory changes, 117 (47%) had positive cultures. Subgroup analysis on individual organisms also showed no significant difference between the two groups. CONCLUSION--Reports of inflammatory changes on cervical smear testing are a poor indicator of infection.     

Studies on the blood of fallow deer (Dama dama) and red deer (Cervus elaphus): haematology, red cell enzymes, metabolic intermediates and glycolytic rates.

1. Blood samples were obtained from fallow deer (Dama dama) and red deer (Cervus elaphus). Basic haematology, red cell enzymes, and metabolic intermediates and the glycolytic rate of the red cells incubated with different substrates were measured. 2. The major findings were (i) the activity of glucose phosphate isomerase was notably high in the red blood cells of the red deer; (ii) red deer cells also utilized adenosine more efficiently than those of fallow deer and (iii) red cells of both species utilized galactose more efficiently than other species of ruminants.     

Effect of garlic oil extract on glutathione reductase levels in rats fed on high sucrose and alcohol diets: A possible mechanism of the activity of the oil

The effect on glutathione reductase activities of feeding garlic oil to white albino rats maintained on high sucrose and alcohol diets was studied. Whereas high sucrose and alcohol diets resulted in significant increases in the activity of glutathione reductase in liver, kidneys and serum, the presence of garlic oil restored the levels to near normal. It is proposed that the mechanism of this action of garlic oil involves the active principle, diallyl disulphide, which interacts in an exchange reaction with enzymes and substrates such as glutathione reductase and glutathione which contain thiol groups.     

Variations in induction of drug-metabolizing enzymes by trans-Stilbene oxide in rodent species

trans-Stilbene oxide (400 mg/kg) produced a 500% increase in the microsomal in the microsomal epoxide hydratase activity in rat and mouse with little change in the soluble enzyme activity. However, in guinea pig, the soluble epoxide hydratase activity increased by about 33% with only a small increase (47.6%) in the microsomal enzyme activity. The soluble glutathione S-transferase activities were also induced in both rat and mouse, with little change in that of the guinea pig. Increasing dosage of trans-stilbene oxide from 400 mg/kg to 1000 mg/kg had little effect on the above enzyme activities. That the guinea pig was not relatively refractory to all inducing agents was shown by the fact phenobarbital (100 mg/kg) and 3-methylcholanthrene (25 mg/kg) produced relatively similar increases in the activities of aniline hydroxylase and P-aminopyrineP-demethylase in rat, mouse and guinea pig. However, these inducers produced only a 15–20% stimulation in the soluble glutathione S-transferase and microsomal epoxide hydratase activities in guinea pig, when compared to a 50–80% increase in rat and mouse, suggesting a general resistance to induction by the phase II enzymes in guinea liver. In all animal models, the inducer markedly increased th emicrosomal total phospholipid content, although the sphingomyelin content itself was decreased. In both rat and mouse, the microsomal cholesterol content was significantly decreased while that in guinea pig was unaffected. Possible factors responsible for the observed species differences are discussed.