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Biochemical characterization of chitotriosidase enzyme: comparison between normal individuals and patients with Gaucher and with Niemann-Pick diseases.

OBJECTIVES: The aim of the present study was to establish the range of chitotriosidase (CT) activity in normal individuals, patients with Gaucher disease (GD) and Niemann-Pick disease (NPD), types A or B. The kinetics of CT in these three groups was also investigated. DESIGN AND METHODS: CT activity, as well as Km, Vmax, optimum pH, and thermal stability of the enzyme were determined in the plasma of control, GD, and NPD subjects. RESULTS: CT activity in GD and NPD patients was, respectively, around 600-fold and 30-fold greater than in normal individuals. We observed significant differences in optimum pH, Vmax, and thermal stability between the various groups. Km was different in normal individuals relative to GD and NPD patients. However, there was no significant difference between Km values in patients with GD and with NPD. CONCLUSIONS: Based on the differences found in the biochemical parameters studied, our results may be important to help the identification of patients not only with GD but also with NPD.

Biological Assay↗

Early detection of cardiac dysfunction in patients with anorexia nervosa by tissue Doppler imaging.

BACKGROUND: Cardiac damage is a major complication of chronic starvation. The aim of this study was to evaluate the changes of left ventricular function in patients with anorexia nervosa by means of pulsed tissue Doppler imaging. METHODS: A total of 20 females (age 22.4+/-4.3 years) with overt anorexia nervosa, 20 matched healthy thin females with body mass index < 19 kg/m2 and 20 matched healthy normal-weight females underwent both standard echocardiography and tissue Doppler imaging. Myocardial systolic wave (Sm) and early (Em) and atrial (Am) diastolic waves were measured on the basal lateral segment and the basal interventricular septum from the apical four-chamber view. RESULTS: When compared with control groups, the anorexia nervosa group showed lower left ventricular mass (p < 0.0001), lower Sm peak of both lateral wall (6.5+/-0.9 vs. 9.4+/-2.1 and vs. 9.5+/-1.9 cm/sec, p < 0.001) and septum (5.6+/-1.5 vs. 8.6+/-1.6 and vs. 8.8+/-1.5 cm/sec, p < 0.001), and comparable Em, Am and Em/Am ratio. The ratio between transmitral peak E and Em was significantly greater in anorexic patients than in controls (lateral wall: 8.1+/-0.1 vs. 6.8+/-0.2 and vs. 6.9+/-0.2, p < 0.001; septum: 10.8+/-0.4 vs. 8.8+/-0.5 and vs. 8.8+/-0.3, p < 0.001). No differences were observed between thin and normal-weight females. In the anorexia nervosa group, S(m) peak was significantly related to left ventricular mass indexed, at both septum (r = 0.55, p < 0.02) and lateral wall (r = 0.49, p < 0.03) levels. CONCLUSIONS: These results show that anorexia nervosa is associated with left ventricular systolic dysfunction, which is related with the reduction of cardiac mass. Tissue Doppler imaging can give useful information in the identification of regional left ventricular dysfunction, in addition to traditional parameters.

Adult↗

Androgen deprivation-induced changes in prostate anatomy predict urinary morbidity after permanent interstitial brachytherapy.

PURPOSE: To evaluate the cytoreductive consequences of neoadjuvant androgen deprivation therapy on International Prostate Symptom Score (IPSS) normalization, catheter dependency, and the need for surgical intervention secondary to bladder outlet obstruction after permanent interstitial brachytherapy. METHODS AND MATERIALS: A total of 116 patients (median follow-up, 30 months) with preandrogen and postandrogen deprivation therapy ultrasound studies and no history of preimplant transurethral resection of the prostate were evaluated. Androgen deprivation-induced changes in prostate volume, transition zone (TZ) volume, and urethral location were correlated with IPSS resolution, catheter dependency, and the need for postimplant surgical intervention. Prostate gland and TZ dimensions and volumes were measured by prolate ellipsoid calculation from the static ultrasound images. The urethral location was determined by identification of a urinary catheter. Additional clinical, treatment, and dosimetric parameters evaluated included patient age, pretreatment prostate-specific antigen, Gleason score, clinical T stage, preimplant IPSS, pre- and postandrogen deprivation ultrasound studies, treatment planning volume, supplemental external beam RT, isotope, total implant activity, Day 0 maximal dose received by 90% of the prostate gland, Day 0 percentage of prostate volume receiving 100%, 150%, and 200% of the prescribed minimal peripheral dose, and urethral dose. RESULTS: For hormonally manipulated patients, the prostate volume at implantation did not have a statistical influence on the percentage of patients returning to IPSS baseline, the time for IPSS normalization, the incidence of catheter dependency, the catheter-dependency time, or the need for postimplant surgical intervention. However, when compared with the hormone-naive cohort, hormonally manipulated patients were more likely to undergo postimplant surgical intervention (5.2% vs. 0.3%, p = 0.001). Greater androgen deprivation-induced reductions in prostate and TZ volumes, along with movement of the urethra closer to the posterior border of the prostate gland, resulted in a decreased incidence of postimplant urinary morbidity. Using Cox regression analysis, the time to IPSS resolution was best predicted by the percentage of TZ volume reduction. Stepwise linear regression analysis demonstrated that the catheter-dependency time was best predicted by the prehormonal therapy prostate volume, posthormonal therapy TZ volume, and the change in the urethral position; prolonged catheter dependency by the percentage of TZ volume reduction, prehormonal therapy TZ index, and the change in the urethral position; and the need for postimplant surgical intervention by the posthormonal therapy TZ index and the change in the urethral location. CONCLUSION: After neoadjuvant androgen deprivation therapy for volume reduction, some brachytherapy-related urinary morbidity parameters are highly related to the preandrogen deprivation prostate volume, variants in the TZ volume, and changes in the urethral location.

Analysis of Variance↗

When is a word a word?

Although adult-based words co-occur in the period of transition to speech with a variety of non-word vocalizations, little attention has been given to the formidable problem of identifying these earliest words. This paper specifies explicit, maximally 'inclusive' identification procedures, with criteria based on both phonetic and contextual parameters. A formal system for evaluating phonetic match is suggested, as well as a set of child-derived functional categories reflecting use in context. Analysis of word use across two samples of 10 children each, followed from 0;9 to 1;4, provides evidence to suggest that context-bound words can be 'trained' by focusing on eliciting language, but that the timing of context-flexible word use remains independent of such training.

Child Language↗

Structure-related statistical singularities along protein sequences: a correlation study.

A data set composed of 1141 proteins representative of all eukaryotic protein sequences in the Swiss-Prot Protein Knowledge base was coded by seven physicochemical properties of amino acid residues. The resulting numerical profiles were submitted to correlation analysis after the application of a linear (simple mean) and a nonlinear (Recurrence Quantification Analysis, RQA) filter. The main RQA variables, Recurrence and Determinism, were subsequently analyzed by Principal Component Analysis. The RQA descriptors showed that (i) within protein sequences is embedded specific information neither present in the codes nor in the amino acid composition and (ii) the most sensitive code for detecting ordered recurrent (deterministic) patterns of residues in protein sequences is the Miyazawa-Jernigan hydrophobicity scale. The most deterministic proteins in terms of autocorrelation properties of primary structures were found (i) to be involved in protein-protein and protein-DNA interactions and (ii) to display a significantly higher proportion of structural disorder with respect to the average data set. A study of the scaling behavior of the average determinism with the setting parameters of RQA (embedding dimension and radius) allows for the identification of patterns of minimal length (six residues) as possible markers of zones specifically prone to inter- and intramolecular interactions.

Amino Acid Sequence↗

Analysis of European and north american maize inbred and hybrid lines by monolithic and perfusion reversed-phase high-performance chromatography and multivariate analysis.

Monolithic and perfusion RP-HPLC methods have been employed for the separation of maize proteins from several European and North American inbred and hybrid lines in analysis times close to 4 min for the perfusion column and close to 8 min for the monolithic column. A study of the repeatability of the protein extraction conditions and of the perfusion and monolithic RP-HPLC methods was performed, indicating low values of variance for the relative peak areas and for the retention times. On the other hand, a low inter-kernel variability of these chromatographic parameters was also found, confirming the possibility of a variety identification and classification of maize inbred and hybrid lines by using a RP-HPLC analysis of the maize proteins. A multivariate analysis of the chromatographic data was carried out in order to characterize and identify the inbred and hybrid maize lines. Cluster analysis of the data showed how far or closely related were the maize lines. Principal component analysis showed that protein chromatographic data had enough information to distinguish between the different groups of maize lines. Finally, a linear discriminant analysis enabled the correct classification of the inbred and hybrid lines according to their geographical origin showing the best percentage of cases correctly classified for monolithic RP-HPLC.

Chromatography, High Pressure Liquid↗

Vanadyl as a probe of the function of the F1-ATPase-Mg2+ cofactor.

The Mg2+ dependent asymmetry of the F(1)-ATPase catalytic sites leads to the differences in affinity for nucleotides and is an essential component of the binding-change mechanism. Changes in metal ligands during the catalytic cycle responsible for this asymmetry were characterized by vanadyl (V(IV) + O)2+, a functional surrogate for Mg2+. The (51)V-hyperfine parameters derived from EPR spectra of VO2+ bound to specific sites on F(1) provide a direct probe of the metal ligands. Site-directed mutations of metal ligand residues cause measurable changes in the (51)V-hyperfine parameters of the bound VO2+, thereby providing a means to identification. Initial binding of the metal-nucleotide to the low-affinity catalytic site conformation results in metal coordination by hydroxyl groups from the P-loop threonine and catch-loop threonine. Upon conversion to the high-affinity conformation, carboxyl groups from the Walker homology B aspartate and MF(1)betaE197 become ligands in lieu of the hydroxyl groups.

Animals↗

[Objective test of smell with cognitive potentials].

BACKGROUND: An objective smelling test is indicated for a reliable assessment of olfactory disorders. Usually olfactory evoked potentials (OEP) are registered. But the technique of this measurement is complicated and the generation of the OEP depends on the respiration of the subject. Alternatively, the contingent negative variation (CNV) can be used in the diagnosis of anosmia and parosmia, requiring only a simple olfactory stimulator. SUBJECTS AND METHOD: OEP and CNV were derived from 25 adults with normal smelling and from 16 patients with anosmia after head injury. First, the "direct" CNV was registered when the subjects expected a tone following a smell stimulus after 1.5 s. Using two different odors in a random order, the tone only followed one of them, so the "selective" CNV was scored. RESULTS: In both tests a distinct CNV was found in 21 and 23 normal smelling subjects, respectively. OEPs were absent in 4.3 % of this control group. No patient with anosmia showed an OEP or a CNV. The amplitudes of the "selective" CNV are significantly higher than those of the "direct" CNV. No gender dependency was found. CONCLUSION: The results show that an objective olfactometry can be realized by registration of CNV. Contrary to the measurement of OEP which depend on the physical parameters of olfactory stimuli, CNV correlates well with the cognitive identification of odor.

Adult↗

A theory of light-induced explosion.

This paper presents a theoretical analysis, based on a simplified one-dimensional model, of the response of an explosive to a wide range of light intensities. A primary result has been the identification and development of a relationship among the important critical parameters. Numerical results illustrating the relationship among the critical light intensity, sample dimension, and ambient temperature have been obtained, with lead azide as the example.

Journal Article↗

Alterations in erythrocyte membrane lipids induced by low doses of ionizing radiation as revealed by 1,6-diphenyl-1,3,5-hexatriene fluorescence lifetime.

Damage in membrane lipids induced by low doses of ionizing radiation in the presence of oxygen has been detected in rabbit erythrocyte ghosts labelled with 1,6-diphenyl-1,3,5-hexatriene (DPH). Multifrequency phase and modulation fluorometry was used to measure DPH fluorescence lifetime. This technique is particularly suited for the observation of heterogeneous fluorescence decays. DPH decay in erythrocyte membranes is described by a two-component continuous distribution of lifetimes. The value of the distribution width of the long-lived component is found to be affected by radiation-induced membrane lipid damage at doses as low as 0.5 Gy, well within the dose range used to measure cell survival. The width of the DPH lifetime distribution decreases when the ghosts are irradiated in the presence of oxygen. Such a decrease is a linear function of the logarithm of the dose. After a dose of 110 Gy and above, the fractional intensity of the short-lived component of the DPH decay increases linearly, indicating severe membrane damage. Experiments performed in the absence of oxygen do not show any change in the fluorescence parameters up to a dose of 550 Gy. The molecular identification of the produced damage has not been accomplished, but the necessity of oxygen to observe the damage suggests that hydroperoxides and lipids crosslinks are produced.

Animals↗

Noninvasive quantification of respiratory modulation on left ventricular size and stroke volume.

To noninvasively explore the complex interactions between heart rate, left ventricular (LV) stroke volume (SV) and respiration, different techniques were proposed and applied to the beat-to-beat measurements of end-diastolic (ED), end-systolic (ES) volumes and SV, obtained from echocardiographic acoustic quantification LV volume signal. Data were obtained from eight patients with dilated cardiomyopathy (DCM, age 60 +/- 2, mean +/- SE), and from 11 age-matched healthy volunteers (N, age 63 +/- 2). Spectral analysis showed an increase in HF power in DCM, both in ED (in ml2, 58 +/- 18 versus 19 +/- 5 in N) and in SV (in ml2, 55 +/- 12 versus 17 +/- 5 in N), together with an increase in total power (in ml2, ED: 119 +/- 31 in DCM versus 48 +/- 9 in N; SV: 88 +/- 17 in DCM versus 31 +/- 8 in N). Folded scattergrams evidenced higher amplitude oscillations in DCM (in ml, ES: 7.93 +/- 1.29; ED: 7.94 +/- 1.59; SV: 7.27 +/- 0.91) compared to N (in ml, ES: 4.08 +/- 0.64; ED: 3.56 +/- 0.65; SV: 3.63 +/- 0.43). Moreover, the prevalent effect of increased afterload generating SV reduction during inspiration was pointed out in N, while an intersubject dispersion in the relation between respiratory phase and LV dimension changes was found in DCM. Black-box model identification summarized these mechanisms by means of a few quantitative parameters.

Cardiomyopathy, Dilated↗

Flow-cytochemical differential leukocyte analysis with quantitation of neutrophil left shift. An evaluation of the Cobas-Helios analyzer.

The Cobas-Helios (Roche Diagnostic Systems, Inc., Branchburg, NJ) is a new, fully automated hematology analyzer that performs a complete blood count and differential leukocyte count (DLC), classifying leukocytes by flow-cytochemical technology. The DLC component of the Cobas-Helios was evaluated according to the National Committee for Clinical Laboratory Standards H20-A protocol. Instrument performance was acceptable with respect to all parameters investigated, including imprecision, inaccuracy and clinical sensitivity for the identification of quantitative and qualitative leukocyte abnormalities. In a minority of samples with neutrophil left shift, neutrophils tended to overlap the monocyte domain, resulting in overestimation of monocytes and underestimation of neutrophils. This problem did not affect clinical sensitivity and was generally associated with a positive instrumental left-shift flag. Flags for the identification of specific qualitative abnormalities of the leukocyte population (atypical lymphoid cells, nucleated red cells, blast cells, immature granulocytes and neutrophil left shift) performed well. In addition to a conventional five-part DLC, the Cobas-Helios also identifies and quantitates atypical lymphoid cells and "large immature cells," the latter corresponding to bands and immature granulocytes. Counts of atypical lymphoid cells and large immature cells correlated well with the equivalent cell classes as enumerated by the reference method of the National Committee for Clinical Laboratory Standards. The Cobas-Helios offers the most reliable quantitative index of neutrophil left shift currently available in a commercial automated DLC analyzer.

Bias↗

Description of ordered solvent molecules in a platinated decanucleotide duplex refined at 1.6A resolution against experimental MAD phases.

Accurate experimental phases derived from a MAD experiment may be useful to enable the identification of solvent molecules during the course of an atomic parameter refinement. The structure of a double-stranded DNA decanucleotide bearing a cisplatin interstrand cross-link at 1.6A resolution, whose phases were first determined experimentally using the L(III) edge of the Pt atom, was refined by various methods. The previously published structure resulted from a least-squares refinement using the structure-factor magnitudes and stereochemical restraints (program SHELX). In this paper, these previous results are compared with a model obtained by the likelihood-maximization method (program REFMAC) which allows the combination of the observed magnitudes with experimental MAD phases. This solution corresponded to a lower R(free) (18.8 compared with 20.3%), a lower R factor and accounted for 135 water molecules and one spermine molecule collected by the program wARP during refinement. The previously published SHELX solution exhibited no spermine molecule and accounted for 92 water molecules, only 74 of which are also present in the model obtained with the MAD phases. In order to verify that these improvements were actually related to the use of the MAD phases, the same type of procedure without the MAD phases was applied starting from the initial model. The resulting solution had a higher R(free) (20.3%), which could be related to the loss of 22 water molecules and the addition of 20 new ones. MAD phases therefore seem especially helpful in preventing the model bias which may affect the solvent molecules. All models have in common a hydration cage of nine water molecules which surround the platinum residue. In addition to the spermine molecule, the model obtained with the MAD phases allows description of the water-molecule organization, with reproducible motifs related to the base pairs and to the phosphodiester backbone.

Base Pairing↗

A decision guideline for emergency department utilization of noncontrast head computed tomography in HIV-infected patients.

OBJECTIVE: To determine which neurologic signs or symptoms are predictive of new focal lesions on head CT in HIV-infected patients. METHODS: Prospective study with convenience sample enrollment of HIV-infected patients who presented to a large inner-city university-based ED over an 11-month period. Patients were assessed using a standardized neurologic evaluation to ascertain whether they had developed new or changed neurologic signs or symptoms. Patients with any new or changed neurologic findings had a head CT scan in the ED. The association between individual complaints or findings and new focal lesions on head CT was assessed by univariate analysis, and sensitivity, specificity, and positive predictive values were calculated. Stepwise logistic regression analysis was then carried out to estimate the relative risk for those variables independently associated with new focal lesions on CT scans. A decision guideline was developed incorporating those variables. RESULTS: One hundred ten patients were identified as having new or changed neurologic signs or symptoms and had a head CT done in the ED. Twenty-seven patients (24%) had focal lesions on head CT, of which 19 (18%) were identified as new focal lesions; eight of these (7%) demonstrated a mass effect. Clinical findings most strongly associated with new focal findings on head CT were: 1) new seizure, relative risk (RR) = 73.5, 95% CI = 6.2 to 873.0; 2) depressed or altered orientation, RR = 39.1, 95% CI = 4.6 to 330.0; and 3) headache, different in quality, RR = 27.0, 95% CI = 3.2 to 230.1. Use of these three findings as a screen for ordering head CT in the ED would have identified 95% (18/19) of the patients with new focal intracranial lesions, and resulted in a 53% reduction in the number of head CTs ordered in the ED. Inclusion of one additional parameter (prolonged headache, > or =3 days), would have resulted in identification of 100% of all new focal lesions, with a 37% reduction in the number of head CTs ordered. Among those patients with new focal findings, 74% required emergent management (i.e., seizure control, IV antibiotics, IV steroids or surgery). The most common intracranial lesion among patients with CD4 counts less than 200 cells/microL was toxoplasmosis, while cerebrovascular accidents (ischemic or hemorrhagic) were most common in those with CD4 counts greater than 200 cells/microL. CONCLUSION: Specific clinical signs and symptoms were associated with the presence of new intracranial lesions in a group of HIV-infected patients who presented to the ED with neurologic complaints. These clinical findings can be incorporated into guidelines for determining the need for emergent head CT. Validation and widespread application of these guidelines could result in limiting the use of emergent neuroimaging to a more well-defined HIV-infected patient population.

AIDS Dementia Complex↗

Electrophoretic determination of sulfhydryl groups and its application to complex protein samples, in vitro protein synthesis mixtures, and cross-linked proteins.

Without prior fractionation, the number of sulfhydryl groups of individual polypeptides in a protein mixture can be determined, provided their molecular weights and approximate isoelectric points are known. Urea-denatured protein samples are reacted with iodoacetamide and iodoacetate in a modified version of Creighton's procedure. After separation by sodium dodecyl sulfate - polyacrylamide gel electrophoresis and isoelectric focusing, the number of sulfhydryl groups is determined by counting the protein bands which have additional negative charges. This method requires little material and provides an additional parameter, besides the molecular weight and isoelectric point, for the identification and characterization of a protein. The sensitivity may be enhanced for nonradioactive proteins by using 14C-labeled iodoacetamide and iodoacetate. The procedure has been applied to prokaryotic in vitro protein synthesis mixtures, bacterial membrane protein, and trypsin-cleaved or chemically cross-linked subunits of the F1 ATPase from Escherichia coli.

Cross-Linking Reagents↗

Failure of platelet parameters and biomarkers to correlate platelet function to severity and etiology of heart failure in patients enrolled in the EPCOT trial. With special reference to the Hemodyne hemostatic analyzer. Whole Blood Impedance Aggregometry for the Assessment of Platelet Function in Patients with Congestive Heart Failure.

Data from small studies have suggested the presence of platelet abnormalities in patients with congestive heart failure (CHF). We sought to characterize the diagnostic utility of different platelet parameters and platelet-endothelial biomarkers in a random outpatient CHF population investigated in the EPCOT ('Whole Blood Impedance Aggregometry for the Assessment of Platelet Function in Patients with Congestive Heart Failure') Trial. Blood samples were obtained for measurement of platelet contractile force (PCF), whole blood aggregation, shear-induced closure time, expression of glycoprotein (GP) IIb/IIIa, and P-selectin in 100 consecutive patients with CHF. Substantial interindividual variability of platelet characteristics exists in patients with CHF. There were no statistically significant differences when patients were grouped according to incidence of vascular events, emergency revascularization needs, survival, or etiology of heart failure. Aspirin use did not affect instrument readings either. PCF correlates very poorly with whole blood aggregometry (r(2) = 0.023), closure time (r(2) = 0.028), platelet GP IIb/IIIa (r(2) = 0.0028), and P-selectin (r(2) = 0.002) expression. Furthermore, there was no correlation with brain natriuretic peptide concentrations, a marker of severity and prognosis in heart failure reflecting the neurohumoral status. Patients with heart failure enrolled in the EPCOT Trial exhibited a marginal, sometimes oppositely directed change in platelet function, challenging the diagnostic utility of these platelet parameters and biomarkers to serve as useful tools for the identification of platelet abnormalities, for predicting clinical outcomes, or for monitoring antiplatelet strategies in this population. The usefulness of these measurements for assessing platelets in the different clinical settings remains to be explored. Taken together, opposite to our expectations, major clinical characteristics of heart failure did not correlate well with the platelet characteristics investigated in this study.

Aged↗

Effect of self-medication with antimalarial drugs on malaria infection in pregnant women in South-Western Nigeria.

OBJECTIVE: To determine the effect of self-medication with chloroquine and pyrimethamine on malaria infection and anaemia during pregnancy. SUBJECTS AND METHODS: The study involved 210 women who attended Ade Oyo Maternity State Hospital, Ibadan, Nigeria. Of these, 156 were pregnant women while 54 were not pregnant (controls). Of the pregnant women, 66 were primigravidae, while 90 were multigravidae. History of treatment of malaria with antimalarial drugs was obtained from the subjects. Gravidity and gestation period were also documented. Two millilitres of blood was withdrawn from each subject, for haematological parameters. Thin and thick films were prepared for malaria parasite identification and quantification. RESULTS: Of the primigravidae and multigravidae 68 and 16.4%, respectively, had taken antimalarial drugs prior to booking. Among primigravidae, only 18% of those with drugs compared with 32% without drugs were malaria-positive. The parasite density was significantly lower among those who took antimalarial drugs than among those who did not (976 +/- 60 versus 2,421 +/- 78, p < 0.05). Similarly, among multigravidae, only 16.4% of those who took antimalarial drugs compared with 34% of those who were not malaria-positive. The parasite density was also significantly lower in multigravidae with drugs than among those without drugs (350 +/- 45 versus 1,000 +/- 65, p < 0.05). The prevalence of anaemia (packed cell volume, PCV < 33) was high, 89% in primigravidae and 70% in multigravidae. Severe anaemia (PCV < 21) was more common in malaria-positive primigravidae and multigravidae than in malaria-negative women. CONCLUSION: The findings indicate that self-medication with chloroquine and pyrimethamine at booking was able to reduce the prevalence of malaria and anaemia in pregnancy.

Anemia↗

Ultrastructural alterations of megakaryocytes in some hematologic disorders.

Bone marrow and peripheral blood samples of patients affected by hematologic disorders involving the megakaryocytic line were examined at the electron microscope. While in idiopathic thrombocytopenic purpura the megakaryocytes appeared almost normal, in primary thrombocythemia there were various ultrastructural alterations interpreted as a counterpart of ineffective thrombocytopoiesis. In one patient with blastic chronic myeloid leukemia and in another with acute megakaryoblastic leukemia, the electron microscope study was very useful in the identification of immature megakaryocytes. In fact, analysis of various ultrastructural parameters allowed some blast cells to be attributed to the megakaryocytic series. Furthermore, platelet demarcation system abnormalities and alterations of the circulating thrombocytes confirm the hypothesis that there is a block in megakaryocytic maturation.

Blood Platelets↗