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Biomedical subjects

E Pozzoli

Publications and source records attributed to E Pozzoli.

At least 19 recordsLinked to original sources

Incidence and histological features of bone marrow involvement in malignant lymphomas.

Bone marrow biopsy (BMB) is a routine investigation in the diagnosis and staging of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL), and there is evidence supporting its prognostic importance in some histological varieties. The histological characteristics of BMB in 433 NHL and 155 HD patients were reviewed for clinicopathological correlations; 36 of these cases were also studied by means of immunohistochemistry. BM infiltrates were discovered in 171 NHL patients. In 36 cases, the diagnosis of NHL was directly established by BMB; a discordance between lymph node and BM histology was observed in 38 of the other 135 cases. BM-positive centroblastic and immunoblastic NHL were significantly associated with larger infiltrates, BM fibrosis, and megakaryocytic hyperplasia. Leukemization at diagnosis was more frequent in low-malignancy NHL. No correlation was found between histology and prognosis, although immunohistochemistry revealed a B-cell phenotype in all but two cases. BMB was positive in 18 of the 155 HD patients and directly diagnostic in two; Reed-Sternberg and Hodgkin cells were CD-30 positive and surrounded by T-cell infiltration. The concordance between BM and lymph node histology was fairly satisfactory, although the relationships between BM infiltration and other histological parameters may reflect peculiar interactions with BM microenvironmental factors. The usefulness of BMB in the diagnosis of malignant lymphomas has been demonstrated, and further progress can be expected from the availability of reliable immunohistochemical markers of clonality reacting on paraffin-embedded BM sections.

Antigens, CD

Heritability estimate of erythrocyte Na-K-Cl cotransport in normotensive and hypertensive families.

Na-K-Cl cotransport was measured in 209 essential hypertensive patients (EH) and in 114 normotensive controls (NT). The distribution of Na-K-Cl cotransport was bimodal in EH and unimodal in NT. The EH with higher Na-K-Cl cotransport values had increased passive permeability to Na in fresh erythrocytes and increased Li-Na countertransport compared to NT. Li-Na countertransport was significantly increased in the EH as a whole, but the increase was accounted for by some EH individuals with elevated Na-K-Cl cotransport values. A simple biometric analysis of the Na-K-Cl cotransport was performed for 287 individuals of 86 families with different prevalence of hypertension (neither parent hypertensive, 39 families; one, 31 families; or both, 16 families). Na-K-Cl cotransport was not correlated between spouses, but was correlated highly significantly between the average value of the two parents (mid-parent) and offspring. The polygenic additive heritability (h2) was about 50% for all families considered together. It increased slightly for the hypertensive families analyzed alone (no significant correlation was found, and hence genetic heritability, in the normotensive families). Finally, after applying arbitrary cut-off points to the Na-K-Cl cotransport values, segregation analysis showed that some major gene, recessive for the high allele, also contributes to the phenotypic value of Na-K-Cl cotransport.

Alleles

Genetic polymorphism of Na-K cotransport in essential hypertension.

Erythrocyte Na-K cotransport is high and genetically correlated to hypertension in Milan hypertensive strain (MHS) rats. In man there is a substantial overlap of individual values between essential hypertensives and controls. However, the findings in rat strains with different types of genetic hypertension suggest that Na-K cotransport studies may throw light on the different pathogenetic mechanisms of the human disease. In 28 normotensive and 22 hypertensive families the midparent-offspring correlation of Na-K cotransport values was significant only in hypertensive families (r = 0.48) and not significant in normotensive ones (r = 0.06), indicating genetic polymorphism for its phenotypic expression only in the hypertensives. In 189 essential hypertensives and 109 normotensives carefully selected from a population-based screening in order to exclude uneven sampling bias, analysis for the bimodality of the distribution of Na-K cotransport clearly showed that normotensives are distributed unimodally and hypertensives bimodally, with nadir of the distributions at about 450 mumols (1 RBC/h). Dividing the hypertensives according to Na-K cotransport value, the high Na-K cotransport subgroup has lower fractional percent excretion of uric acid and plasma renin activity. These data suggest that the high Na-K cotransport subgroup has peculiar characteristics of greater proximal tubular reabsorption (lower fractional excretion of uric acid) that may cause body volume expansion (lower plasma renin activity).

Biological Transport, Active

Scanning electron microscope cytochemistry of blood cells.

The backscattered electron imaging (BEI) mode of scanning electron microscopy (SEM) has been applied to study various histo-cytochemical reactions in biological specimens since the early seventies. Due to numerous, recent technical improvements the BEI mode of SEM now belongs to the routine of many SEM laboratories. For cytochemistry, BEI has been mainly used to: visualize intracellular structures and organelles; recognize the different cell types in heterogeneous populations or tissues; study the correlations between enzymatic activities and cell surface features. We have evaluated the most relevant results obtained in the study of blood cells and the possible future applications of these techniques.

Blood Cells

Cytochemical methods for the backscattered electron imaging mode of scanning electron microscopy: further applications to the study of human leukemic cells.

The Backscattered Electron Imaging (BEI) mode of Scanning Electron Microscopy (SEM) has been applied to the study of cells stained with various heavy metals in cytochemical reactions. Improvements or modifications of some of these methods and their application to the study of normal and leukemic leukocytes have been evaluated in this report. The results obtained after staining peroxidase-positive granules with osmium, copper, cobalt-nickel and gold-cobalt are compared. Granules containing non-specific esterase activity were demonstrated in the BEI mode after incubation of the cells in Hanker medium and staining with osmium. While sites of acid phosphatase activity were easily localized with a conventional lead method, alkaline phosphatase activity was demonstrated only in the phagocytic vacuoles of cells previously incubated with latex particles and subsequently stained with lead. Cell nuclei were identified in the BEI mode after silver methenamine or bismuth staining. Combining their cell surface and cytochemical characteristics a more accurate identification of the different blood cell types with the SEM becomes possible.

Acid Phosphatase

Alkaline phosphatase activity in phagocytizing granulocytes: a backscattered electron imaging study.

The scanning electron microscope (SEM) in the backscattered electron imaging (BEI) mode has been used to detect alkaline phosphatase activity in normal human PMNs using a lead method. Unfortunately commercial scanning electron microscopes do not allow resolution of the small and dispersed lead depositions in the secondary granules. However, polymorphonuclear leukocytes (PMNs) previously incubated with latex particles, show well evident lead precipitates allowing identification of different phases of the phagocytic sequence. In fact the finding of irregular depositions arranged around a central not-emitting zone might be due to the secondary granules gathering near the phagocytic vacuole. Moreover, homogeneous, round, well defined precipitates, having a diameter slightly larger than latex particles, probably corresponding to vacuoles filled with the enzyme after granules coaslescence and fusion.

Alkaline Phosphatase

Ultrastructural study of leukemic cell phagocytosis using the myeloperoxidase reaction.

The phagocytosis (in the absence of serum factors) of zymosan particles by peripheral leukocytes isolated from ten patients with acute leukemia (AMbL, AMoL, AMML, AUL, ALL and CML-BC) was studied at the electron microscope. An evident phagocytic activity was observed only in the cells in which cytochemical and ultrastructural features suggested that the blast elements belonged to the monocytic series. However, no phagocytosis by unclassifiable leukemic blasts was observed, even though they had some submicroscopic characteristics of the monocytic series. These findings suggest that phagocytic capacity develops during the course of cell differentiation, becoming striking only when the blast cell acquires the ultrastructural features of the pro-monocytic stage. Using the myeloperoxidase reaction, this study also demonstrates a morphological alteration in the degranulation process after the ingestion of zymosan particles in both the blasts and the mature PMN cells of leukemic patients. This defect could be related to the susceptibility to severe infections usually found in subjects with hematological malignancies.

Humans

Acute lymphoblastic leukemia: a study of 25 cases by scanning electron microscopy.

Cells from 25 cases of acute lymphoblastic leukemia (ALL) were studied under the scanning electron microscope (SEM). In 24 of the cases, the vast majority of circulating leukaemic cells had few microvilli. Villous cells were rarely encountered and prominent ridge-like profiles and ruffled membranes were not seen. Only six cases were studied by immunological techniques and four of the cases were of the null type while in two the cells bore detectable T-markers. It seems that ALL is almost always associated with the presence of cells with few microvilli in the peripheral circulation, differing in this respect from most cases of CLL. Although circulating leukaemic lymphocytes with few microvilli are sometimes seen in CLL, the most frequent cell type encountered is a more villous lymphocyte. Differences between leukaemic cells from patients with ALL, CLL and non-lymphoblastic leukaemias are discussed. It appears that SEM may help to distinguish lymphoblastic and nonlymphoblastic leukaemic cells in many instances and can be used as a useful adjunct to other modes of microscopy in the diagnosis of acute leukaemia.

Adult

Autoantibodies and spleen cell-mediated cytotoxicity in adriamycin-induced myocardiopathy in rabbits.

Spleen cells from rabbits affected by adriamycin-induced cardiomyopathy were specifically cytotoxic for rabbit embryonic heart cells in microcytotoxicity tests. The interactions between "sensitized" spleen cells and rabbit embryonic heart cells were observed by scanning electron microscopy. Sera from these rabbits were shown by immunofluoresence to contain antibodies reactive with rabbit embryonic heart, kidney, and muscle cells. Cytotoxic antibodies were not detected. These sera contained factors that enhanced the cytotoxicity mediated by "sensitized" spleen cells and made normal spleen cells capable of destroying targets. The detection of these factors and of cytotoxins was dependent on the method of target-effector cells treatment by serum.

Animals

Human platelet aggregation by mixed cryoglobulins.

Glomerulonephritis in idiopatic mixed cryoglobulinemia represents perhaps a glomerular damage by immune complexes. In this study, a sigmoidal-like curve was obtained after addition of 13 different mixed cryoglobulins to both autologous and isologous platelet-rich plasma, tested in platelet aggregometer. The lag phase of the curve corresponds to platelet phagocytosis of cryoglobulin-binding ferritin, as shown in electron microscopy and the optical density decrease phase corresponds to the aggregation of platelets that shows the same ultrastructural characteristics of ADP-induced platelet aggregation. This platelet aggregation is inhibited by different drugs. Intraglomerular platelet aggregation by cryoglobulins might play a key role in determining the glomerular damage in cryoglobulinemia by the release of nucleotides and vasoactive amines.

Blood Platelets

Platelet aggregometry and anti-platelet isoantibodies.

102 sera from polytransfused patients have been screened in platelet aggregometry. Anti-human platelet isoantibodies, tested against 'responsive' human platelets in PRP, give in the aggregometer a decrease in optical density recorded as a sigmoidal curve. In the first step of reaction PF3 availability suggests that the primary action of antibody is to damage the platelet membrane. The second step might be a true aggregation (an ADP-mediated platelet clumping) or a platelet lysis, depending on the type and the potency of antibody, on the type of platelets (normal or thrombasthenic) and on some experimental conditions. These conclusions, confirmed by electron microscopy findings, suggest that aggregometry is a very rapid and simple method of detecting platelet antibodies.

Adenosine