Kinetika i aktivnost leukocitne arilsulfataze A u osoba s dijagnozom cerebralne paralize

Activity and kinetics of arylsulfatase A (ASA, EC 3.1.6.8) were analyzed in leukocyte homogenates derived from patients suffering from cerebral palsy. Lower ASA activity was found in the patients\u27 leukocytes than in controls, as determined by spectrophotometry using chromogenic substrate p-nitrocatechol sulfate (p-NCS). Kinetic parameters, Km and vmax, for leukocyte ASA were determined from the dependence of initial reaction velocities on the p-NCS concentrations. A slight difference in Km values was found for leukocyte enzyme in cerebral palsy (0.26 mmol L-1) compared to the control (0.21 mmol L-1), whereas max-1 value for leukocyte ASA in disease reached only 58% of the control value. In addition, the presence of the most common mutations associated with ASA pseudodeficiency (N350S, 1524+95 A>G) and metachromatic leukodystrophy (P426L) was detected in all investigated patients. Changes in activity and kinetic parameters of leukocyte ASA in cerebral palsy are most probably related to the decrease of enzyme concentration; the detected mutations might at least partially contribute to the observed changes.Analizirane su aktivnost i kinetika arilsulfataze A (ASA, EC 3.1.6.8) u leukocitnim homogenatima osoba oboljelih od cerebralne paralize. Spektrofotometrijskim određivanjem aktivnosti ASA prema kromogenom supstratu p-nitrokatehol sulfatu (p-NCS) utvrđene su manje aktivnosti enzima u leukocitima oboljelih osoba. Kinetički parametri, Km i vmax, leukocitne ASA određeni su iz ovisnosti početne brzine reakcije o koncentraciji p-NCS. Utvrđena je manja razlika između Km vrijednosti enzima zdravih (0,21 mmol L-1) i oboljelih osobal (0.26 mmol L-1), dok je vrijednost vmax enzima iznosila 58% vrijednosti vmax enzima zdravih osoba. Također je u svih ispitanika s dijagnozom cerebralne paralize utvrđeno prisustvo najčešći mutacija povezanih s ASA pseudodeficijencijom (N350S, 1524+95 A>G) i metakromatskom leukodistrofijom (P426L). promjene aktivnosti i kinetičkih parametara leukocitne ASA u cerebralnoj parealizi najvjerojatnije su posljedica snižene koncentracije enzima; moguće je da nađene mutacije barem djelomično doprinose zapaženim promjenama

A global analysis of Y-chromosomal haplotype diversity for 23 STR loci

In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.Peer reviewe

Leukocyte lysosomal enzymes in Alzheimer's disease and Down's syndrome

Previous studies suggested the possibility of accelerated lysosomal degradation of brain gangliosides in Alzheimer's disease (AD). As AD pathology affects both neural and nonneural tissues, the aim of this study was to determine possible changes of glycosphingolipid metabolism in available peripheral cells in AD and Down's syndrome (DS). The activities of several lysosomal enzymes involved in catabolism of gangliosides and sulfatides were measured in leukocytes from subjects with dementia of the Alzheimer type, DS, and age-matched controls, by fluorimetry and spectrophotometry using specific substrates. The results showed a statistically significant increase of beta-galactosidase activity in both dementia of the Alzheimer type and DS leukocytes when compared with age-matched controls (p <.01 and p <.05, respectively; Student's t test). Not significantly increased activities of beta-galactosidase, beta-hexosaminidase, beta-hexosaminidase A, and slightly decreased activity of arylsulfatase A were observed in control leukocytes with aging. Our results indicate that a metabolic dysfunction and the acceleration of at least some lysosomal catabolic pathways are present in AD and DS nonneural cells