Letter confusions and reversals of sequence in the beginning reader: implications for Orton's theory of developmental dyslexia.
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Biomedical subjects
Publications and source records attributed to C Orlando.
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Free radicals are considered to be important factors involved in many physiopathological processes. Several methods have been proposed for studying the mechanisms of antioxidant protection against free radical-induced injury, including the measurement of the total antioxidant capacity (TAC) in body fluids, based on enhanced chemiluminescence. This technique is calibrated against Trolox and assay results are expressed as mumol/L of Trolox equivalents. Since many of the complications induced by diabetes appear to be mediated by oxygen free radical generation, we have investigated serum antioxidant capacity in a group of healthy subjects and in insulin-dependent diabetic (IDDM) subjects. A statistically significant difference was noticed in TAC values between the IDDM group and the young control group. Even if the biological meaning of this significant reduction in TAC remains to be explained, an overproduction of precursors of reactive oxygen free radicals and/or a decreased scavenger systems efficiency can be associated with the increased risk of atherosclerotic cardiovascular disease in diabetic patients.
We present a method for the measurement of the total Somatomedin C (SmC) content in human early morning urine samples after dialysis, extraction, and concentration. We modified a chemiluminescence immunoassay, previously developed for SmC determination in serum, for analysis of SmC in urine. Appropriate sensitivity was obtained by the preparation of a new chemiluminescent tracer (AEEI-COOH-SmC) and the optimization of a competitive non-equilibrium immunoassay system which had a detection limit of 0.24 fmol SmC per tube.
We present an application of image analysis for the direct quantification of PCR products after gel electrophoresis and ethidium bromide staining of DNA. This procedure has been applied to the development of an assay based on competitive PCR for the measurement of the degree of amplification of c-erbB-2 oncogene in DNA from human tumours. In this method two DNA species (genomic and competitor) compete for PCR amplification. Since results are calculated from the final competitor/genomic ratio any variable affecting the rate of PCR amplification has no effect on the accuracy of the ratio measurement. Results are reported which show that even large variations in the experimental conditions (number of PCR cycles, sample volumes and extracted DNA quality) did not interfere with the precision of the measurement of the competitor/genomic ratio.
LDH-X, an isoenzyme of lactate dehydrogenase specific for germinal epithelium activity, has been measured in the seminal plasma of infertile subjects whose infertility had different origins. In the same samples, seminal transferrin, an index of Sertoli cell function, was also measured. In this investigation, seminal LDH-X was not detectable in the vasectomized subjects, in patients with azoospermia due to seminiferous tubular damage, nor in patients who showed a marked decrease in sperm concentration (less than 1 X 10(6)/ml). In oligozoospermic patients (sperm concentration less than 20 X 10(6)/ml) seminal LDH-X levels were reduced to about one-third of those found in normal controls. Seminal LDH-X levels correlated (r = 0.7237) with total sperm count better than seminal transferrin levels (r = 0.5511), while no correlation was found between these two biochemical parameters and sperm motility, viability and morphology. To study their spontaneous variations with time, LDH-X and transferrin were also measured in semen specimens collected monthly from five healthy men, over 1 year. In these samples (N = 60), sperm count variability (43.1%, calculated in terms of the coefficient of variation), was similar to that of LDH-X (40.4%) and higher than for transferrin (23.0%).
The aim of this study was to detect linear arterial calcification (Mönckeberg's sclerosis) localized in feet, ankles, legs, knees and hands in an attempt to correlate the extent of calcification with the presence and severity of autonomic neuropathy as well as with microangiopathy (proliferative retinopathy, proteinuria greater than 200 mg/die) and peripheral neuropathy. Typical linear calcification were observed in 37 out of 41 (90.2%) patients with autonomic neuropathy and in none of those without autonomic neuropathy (p less than 0.001). These 37 patients were divided into two subgroups by cluster analysis: Subgroup A, including 18 subjects with calcification length ranging from 8 to 26 cm and moderate autonomic neuropathy, and Subgroup B, including 19 subjects with calcification length between 58 and 126 cm and severe autonomic neuropathy (p less than 0.0001 by Spearman's test). No difference in the length of arterial calcification was detected between patients with proteinuria greater than 200 mg/24h and/or proliferative retinopathy and patients without these complications. A possible relationship between arterial calcification and peripheral neuropathy is difficult to evaluate; in fact, the majority of subjects having autonomic neuropathy had peripheral neuropathy, too. Vice versa, around 10% of patients without peripheral neuropathy but with autonomic neuropathy did not have Mönckeberg's sclerosis. Autonomic neuropathy is the principal factor responsible for calcification of the arterial media, and in addition the severity of the neuropathy, rather than the patient's age or the known disease duration seems to determine the extent of calcification.
In 9 healthy subjects we evaluated the effect of a constant ranitidine infusion (100 mg) on glucose (mg/dl), insulin (microU/ml) and C-peptide (ng/ml) serum levels promoted by oral glucose tolerance test (75 g). Ranitidine significantly increased the area under concentration/time curves for glucose and insulin but not that of C-peptide. Our data indicate that ranitidine does not affect pancreatic insulin release nor peripheral glucose utilization and are consistent with the hypothesis that ranitidine influences the hepatic clearance of glucose and insulin both of which undergo high first-pass liver extraction.
The purpose of the study described here was to evaluate the relationship between inhibin (INH) and bioactive FSH (B-FSH) or immunoreactive FSH (I-FSH) in oligoazoospermic patients. To accomplish this, the authors measured serum levels of INH, I-FSH, B-FSH, LH and testosterone (T) in 98 male patients attending the andrology Centre at Malphighi Hospital (Bologna) for infertility workup. On the basis of the mean sperm concentration, patients with sperm output > or = 4 x 10(7) ml-1 (n = 30) formed the control group (group A), whereas oligozoospermic patients were divided arbitrarily into three groups. Sperm concentrations for these groups ranged as follows: B, 2-4 x 10(7) ml-1 (n = 14); C, 5 x 10(6)-2 x 10(7) ml-1 (n = 18); D, < 5 x 10(6) ml-1 (n = 17). In addition, the authors studied a group of patients with possible non-obstructive azoospermia (n = 19, group E), confirmed in 16 of them through testicular biopsy. There were no significant differences in serum levels of LH and T among groups. However, azoospermic patients had a significant reduction of the T/LH ratio. Similarly, B-FSH and B/I-FSH ratios were significantly elevated only in group E. INH serum levels did not show any appreciable changes among groups and in azoospermic patients INH correlated significantly and in a positive manner with I-FSH serum levels and negatively with B/I-FSH and T/LH ratios. Within the azoospermic patient group no consistent relationship was evident between INH serum concentration and various degrees of spermatogenetic arrest.(ABSTRACT TRUNCATED AT 250 WORDS)
Sixty 10-mm bone-patellar tendon-bone allografts from young human donors were placed into four test groups, a control fresh-frozen group and three fresh-frozen irradiated groups. The irradiated groups were exposed to 2.0, 3.0, or 4.0 Mrad of gamma irradiation. The specimens were tested to tensile failure. The initial biomechanical strength of fresh-frozen allografts was reduced up to 15% when compared with fresh-frozen controls after 2.0 Mrad of irradiation. Maximum force, strain energy, modulus, and maximum stress demonstrated a statistically significant reduction after 2.0 Mrad of irradiation (P < 0.01). Stiffness, elongation, and strain were reduced but not with statistical significance. A 10% to 24% and 19% to 46% reduction in all biomechanical properties were found after 3.0 (P < 0.005) and 4.0 (P < 0.0005) Mrad of irradiation, respectively. After irradiation with a 4.0 Mrad dose, the ultimate load was below that of reported values for the human anterior cruciate ligament. It is clinically important to observe and document changes in human ligaments that result from currently used doses of gamma irradiation. The results from this study provide important information regarding the initial biomechanical properties of fresh-frozen human bone-patellar tendon-bone allografts after bacterial sterilization with gamma irradiation. The current accepted dose for sterilization is between 1.5 and 2.5 Mrad. There appeared to be a dose-dependent effect of irradiation on all the biomechanical parameters studied. Four of seven parameters were found to be reduced after 2.0 Mrad of irradiation. Reductions were found in all parameters after 3.0 and 4.0 Mrad of irradiation.
Biomarker analysis and evaluation in oncology is the product of a number of processes (including managerial, technical and interpretation steps) which need to be monitored and controlled to prevent and correct errors and guarantee a satisfactory level of quality. Several biomarkers have recently moved to clinical validation studies and successively to clinical practice without any definition of standard procedures and/or quality control (QC) schemes necessary to guarantee the reproducibility of the laboratory information. In Italy several national scientific societies and single researchers have activated -- often on a pilot level -- specific external quality assessment protocols, thereby potentially jeopardizing the clinical reality even further. In view of the seriousness of the problem, in 1998 the Italian Ministry of Health sponsored a National Survey Project to coordinate and standardize the procedures and to develop QC programs for the analysis of cancer biomarkers of potential clinical relevance. Twelve QC programs focused on biomarkers and concerning morphological, immunohistochemical, biochemical, molecular, and immunoenzymatic assays were coordinated and implemented. Specifically, external QC programs for the analytical phase of immunohistochemical p53, Bcl-2, c-erb-2/neu/HER2, and microvessel density determination, of morphological evaluation of tumor differentiation grade, and of molecular p53 analysis were activated for the first time within the project. Several hundreds of Italian laboratories took part in these QC programs, the results of which are available on the web site of the Network (www.cqlaboncologico.it). Financial support from the Italian Government and the National Research Council (CNR) will guarantee the pursuit of activities that will be extended to new biomarkers, to preanalytical phases of the assays, and to revision of the criteria of clinical usefulness for evaluating the cost/benefit ratio.
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Besides the application of conventional qualitative PCR as a valuable tool to enrich or identify specific sequences of nucleic acids, a new revolutionary technique for quantitative PCR determination has been introduced recently. It is based on real-time detection of PCR products revealed as a homogeneous accumulating signal generated by specific dyes. However, as far as we know, the influence of the variability of this technique on the reliability of the quantitative assay has not been thoroughly investigated. A national program of external quality assurance (EQA) for real-time PCR determination involving 42 Italian laboratories has been developed to assess the analytical performance of real-time PCR procedures. Participants were asked to perform a conventional experiment based on the use of an external reference curve (standard curve) for real-time detection of three cDNA samples with different concentrations of a specific target. In this paper the main analytical features of the standard curve have been investigated in an attempt to produce statistical diagnostics emerging from external quality control. Specific control charts were drawn to help biochemists take technical decisions aimed at improving the performance of their laboratories. Overall, our results indicated a subset of seven laboratories whose performance appeared to be markedly outside the limits for at least one of the standard curve features investigated. Our findings suggest the usefulness of the approach presented here for monitoring the heterogeneity of results produced by different laboratories and for selecting those laboratories that need technical advice on their performance.
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We have previously found the presence of endothelin (ET) receptor and ET-like immunoreactivity in rat testis. We now extend our studies from rat to human testis. We found expression of a specific transcript for ET-1 and ET-1-like immunoreactivity in human testis. Positive staining was confined to the Sertoli cells of the tubular compartment, although few peritubular and interstitial cells were also stained. We also identified specific ETA and ETB receptor transcripts in human testis; ETA expression was more abundant than the ETB expression. Mathematical analysis of multiple self- and cross-competition studies among [125I]ET-1, [125I]ET-3, and analogues confirmed the presence of the ETA and ETB isoreceptors. In testicular homogenates, the ETA receptor was sevenfold more concentrated than the ETB receptor. In order to localize the receptors, we performed [125I]ET-1 autoradiography. Binding sites were mostly concentrated into the seminiferous tubules, although interstitial and peritubular myoid cells were also positive. Within the seminiferous tubules, [125I]ET-1 binding sites were confined to primary and secondary spermatocytes and early spermatids, whereas Sertoli cells were negative. We were unable to demonstrate the presence of functional ET receptors in ejaculated spermatozoa. Because ET-like immunoreactivity was present in Sertoli cells, we next asked whether authentic ET-1 is present in human seminal fluid and represents a good index for Sertoli cell function. Reverse-phase high-performance liquid chromatography analysis of ET-like immunoreactivity in seminal fluid indicated that most of the detected peptides correspond to the ET-1 precursor, big-ET-1. The seminal concentration of ET-like immunoreactivity was similar in normospermic, oligospermic, azoospermic, and vasectomized men, indicating that ETs are produced in different parts of the male genital tract and that they do not represent an useful tool for the diagnosis of male reproductive diseases. In conclusion, this study demonstrated, for the first time, the presence of ET-1 and its receptors in human testis.