MALDI imaging mass spectrometry reveals multiple clinically relevant masses in colorectal cancer using large-scale tissue microarrays.

For identification of clinically relevant masses to predict status, grade, relapse and prognosis of colorectal cancer, we applied Matrix-assisted laser desorption ionization (MALDI) imaging mass spectrometry (IMS) to a tissue micro array containing formalin-fixed and paraffin-embedded tissue samples from 349 patients. Analysis of our MALDI-IMS data revealed 27 different m/z signals associated with epithelial structures. Comparison of these signals showed significant association with status, grade and Ki-67 labeling index. Fifteen out of 27 IMS signals revealed a significant association with survival. For seven signals (m/z 654, 776, 788, 904, 944, 975 and 1013) the absence and for eight signals (m/z 643, 678, 836, 886, 898, 1095, 1459 and 1477) the presence were associated with decreased life expectancy, including five masses (m/z 788, 836, 904, 944 and 1013) that provided prognostic information independently from the established prognosticators pT and pN. Combination of these five masses resulted in a three-step classifier that provided prognostic information superior to univariate analysis. In addition, a total of 19 masses were associated with tumor stage, grade, metastasis and cell proliferation. Our data demonstrate the suitability of combining IMS and large-scale tissue micro arrays to simultaneously identify and validate clinically useful molecular marker. Copyright © 2017 John Wiley & Sons, Ltd.

Homogenization of tissues via picosecond-infrared laser (PIRL) ablation: Giving a closer view on the in-vivo composition of protein species as compared to mechanical homogenization.

Posttranslational modifications and proteolytic processing regulate almost all physiological processes. Dysregulation can potentially result in pathologic protein species causing diseases. Thus, tissue species proteomes of diseased individuals provide diagnostic information. Since the composition of tissue proteomes can rapidly change during tissue homogenization by the action of enzymes released from their compartments, disease specific protein species patterns can vanish. Recently, we described a novel, ultrafast and soft method for cold vaporization of tissue via desorption by impulsive vibrational excitation (DIVE) using a picosecond-infrared-laser (PIRL). Given that DIVE extraction may provide improved access to the original composition of protein species in tissues, we compared the proteome composition of tissue protein homogenates after DIVE homogenization with conventional homogenizations. A higher number of intact protein species was observed in DIVE homogenates. Due to the ultrafast transfer of proteins from tissues via gas phase into frozen condensates of the aerosols, intact protein species were exposed to a lesser extent to enzymatic degradation reactions compared with conventional protein extraction. In addition, total yield of the number of proteins is higher in DIVE homogenates, because they are very homogenous and contain almost no insoluble particles, allowing direct analysis with subsequent analytical methods without the necessity of centrifugation. BIOLOGICAL SIGNIFICANCE: Enzymatic protein modifications during tissue homogenization are responsible for changes of the in-vivo protein species composition. Cold vaporization of tissues by PIRL-DIVE is comparable with taking a snapshot at the time of the laser irradiation of the dynamic changes that occur continuously under in-vivo conditions. At that time point all biomolecules are transferred into an aerosol, which is immediately frozen.

[Treatment of newly diagnosed type II diabetic patients with special reference to prescribing glibenclamide in low doses]. / Die Behandlung neuerfasster Typ-II-Diabetiker unter besonderer Berücksichtigung der Verordnung von Glibenclamid in niedriger Dosierung.

In the period of 15 months 90% of all newly registered type II diabetics of a district area (70 males, 122 females) were prospectively thoroughly examined above all in hospital, standardizedly stabilized and have been followed up for 1 year with regard to their therapy behaviour. From the features obtained (age, body weight, heredity, symptomatology, blood glucose and insulin concentrations basally and after 75 g oGTT) subgroupings were worked out relevant for the therapy. 64% of the newly registered type II diabetics could be stabilized purely dietetically (males 70%, females 60.7%). Female type II diabetics revealed the worse course of therapy. Younger age, overweight, genetic load and higher insulin concentrations are markers of the importance of the insulin resistance and a domain of the basis therapy. Older age, normal weight in connection with higher blood glucose and lower insulin concentrations as an expression of the insulin deficit of higher degree render in most cases possible a treatment with SH-preparations. Small doses of glibenclamide proved to be very favourable both in not purely dietetically manageable younger patients and in older patients. 68% of all SH-cases did with a dosage of 1-3 mg glibenclamide a day, 28% with 1 mg a day. The pathophysiologic and pharmacologic mechanisms are discussed.

[Lipid parameters in newly detected type II diabetic patients and relations to coronary heart disease]. / Lipidparameter bei neuerfassten Typ-II-Diabetikern und Beziehungen zur koronaren Herzkrankheit.

In a prospective study 192 new manifested type 2 (noninsulin dependent) diabetics were checked in view of prevalence of coronary heart disease (CHD) and hypertension in relation to concentration of lipids in serum. CHD was found in 49%, hypertension in 53% dominating females. Increased triglycerides (1.98 mmol/l) and decreased HDL-cholesterol i.s. (1.28 mmol/l) were characteristically, cholesterol (6.6 mmol/l) were within references, the lipoprotein-screening test was pathologically. Prevalence of CHD was associated with age, sex, hypertension, partly with triglycerides and weight and inverse with HDL-cholesterol i.s. but not with the concentration of blood glucose and insulin i.s. basal as well as stimulated (75 g oGTT). In conformity with other studies the differences in lipids alone would'nt be allowed to explain the high prevalence of CHD in new manifested type 2 diabetics.