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Detection of posttranslational modifications is expected to be one of the major future experimental challenges for proteomics. We describe herein a mass spectrometric procedure to screen for protein modifications by peptide mass fingerprinting that is based on post-data acquisition improvement of the mass accuracy by exporting the peptide mass values into analytical software for multipoint recalibration on recognized peaks. Subsequently, the calibrated peak mass data set is used in searching for modified peptides, i.e., peptides possessing specific mass deviations. In order to identify the location of Lys- and Gln-residues available for transglutaminase-catalyzed isopeptide bond formation, mammalian small heat shock proteins (sHsps) were screened for labeling with the two hexapeptide probes GQDPVR and GNDPVK in presence of transglutaminase. Peptide modification due to cross-linking of the GQDPVR hexa-peptide probe was detected for C-terminal Lys residues. Novel transglutaminase-susceptible Gln sites were identified in two sHsps (Q31/Q27 in Hsp20 and HspB2, respectively), by cross-linking of the GNDPVK hexapeptide probe. Deamidation of specific Gln residues was also detected, as well an isopeptide derived from intramolecular Gln-Lys isopeptide bond formation. We conclude that peptide mass fingerprinting can be an efficient way of screening for various posttranslational modifications. Basically any instrumentation for MALDI mass spectrometry can be used, provided that post-data acquisition recalibration is applied.
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The investment going into stem-cell therapies and technologies is impressive. The objectives are great, including the aim of tissues on demand within 20 years, and the rewards potentially huge with a suggested annual market of US dollar 500 billion. This article outlines current activities on both sides of the Atlantic.
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Until the early nineteenth century, diabetes mellitus was regarded as a disease of the kidney, in which there was an increase in the volume of urine and a wasting of the flesh. With the identification of glucose in blood and urine in the late eighteenth century, first it was re-framed as a disease of assimilation and only then became a metabolic disorder. Whilst these changing concepts were debated, it was noted in parallel that diabetics might show coagulable urine containing albumin, even before Bright and others had established this as a sign of kidney disease. Wilhelm Griesinger (1817-1868) was perhaps the first to suggest in 1859 that the diabetes might be causing the Bright's disease, with the latter as a 'complication'. During the next half-century the observation that as albuminuria appeared and increased, so glycosuria improved or might remit, with a parallel or subsequent evolution into uraemia. Glomerulosclerosis and arteriolosclerosis were described in occasional patients during the same period, but text-books of pathology ignored these observations. Thus it was only when diabetics began to survive longer using insulin treatment in the early 1920s that a diabetic nephropathy became widely recognized. After a few isolated descriptions which were ignored, the now famous paper of Paul Kimmelstiel and Clifford Wilson appeared in 1935 detailing nodular renal lesions in just 8 maturity-onset (48-68 year old) diabetics. They barely noted the association with diabetes however, and it was Arthur Allen in 1941 who clarified the association in 105 patients with diabetes, again all aged over 40. Despite the age of the patients in these early studies, diabetic nephropathy became thought of as a disease of young diabetics as a cohort of survivors of juvenile diabetes passed 15 years or more of disease and more than half developed nephropathy. In the 1950s the technique of renal biopsy was rapidly applied to the study of diabetics, and the early lesions defined using electron microscopy as well as optical methods. Then the role of diabetic nephropathy as a cause of renal failure changed: to begin with numbers of young insulin-requiring diabetics were small and infrequently referred for dialysis treatment or transplantation. Then in the 1970s and 1980s the proportion of such juvenile-onset diabetics developing renal failure gradually fell, but at the same time much larger numbers of older diabetics survived their vascular disease and required treatment for renal failure. World-wide, today diabetes accounts for 20-50% of patients entering established renal failure programs, and absolute numbers increase as greater longevity and western-style living has promoted an 'epidemic' of diabetes at all ages.
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The purpose of this text is to search for medical books in monasteries, museums and university libraries in Split, Omi's, Zaostrog, Ciovo (near Trogir) and Sinj. Medical books from the 17th century were rare. When we compare this research with previous ones, one can conclude that very little of such sort of literature in Dalmatian libraries is still existing. Among preserved literary works we found works by Galenus, Oribasius, Valverde and others. The explanation for the little number of medical books is to be seeked in hard historical and educational conditions, destruction and damage to library stock in the past.
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The author analyzed reports on the mentally sick and psychiatry in our daily newspapers in 1909, 1928 and 1960. He analyzed the number, type, terminology and general character of the informations. In 1909 and 1928 he found a large number of references; their number and subjects were not very dependent on the type of paper nor on the year of publication. Roughly one quarter of the mentioned reports was information on the heteroaggressiveness of the mentally sick which naturally evoked negative attitudes of the public. Reports evoking positive attitudes, e.g. sympathy, were very rare. From the psychopathological aspect most frequently accounts on psychoses were found. In descriptions of the symptomatology the author did not detect any attempts of professional or pseudoprofessional accounts. In 1960 no data were found. We assume that at present when there is an increased interest in the press in psychiatric problems the historical retrospective may prove useful for the under standing of some unfavourable attitudes of the public to psychiatry as well as for possible reflections on improvement of the unsatisfactory attitude of the public to the discipline of psychiatry.