Diagnosis of leukemia: morphology.
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Humans↗
Biomedical subjects
F Lanza
Publications and source records attributed to F Lanza.
Immunogenotypic characteristics of chronic lymphocytic leukemia patients from northern Italy.
Ig gene analysis, carried out in 25 patients failed to show rearrangement patterns typical of each stage, but, nevertheless, confirmed the monoclonal origin of leukemic cells in these patients. In addition, in 14 of them the pattern of Ig gene rearrangements measured on two different occasions was analyzed. Only in patients who had received chemotherapy, the intensity of the Ig germline band was greater than that of the rearranged bands, indicating the reduction of lymphocytosis after the therapy. Thus, though Ig gene rearrangement could not distinguish the CLL stage, our data confirm the usefulness, at all clinical stages, of Ig gene analysis as a tool in the evaluation of the efficiency of the therapy.
Antibodies, Monoclonal↗
Differential effects of extra- and intracellular calcium chelation on human platelet function and glycoprotein IIb-IIIa complex stability.
The presence of extracellular ionized calcium (Ca2+) is important to support the aggregation of human blood platelets and for the stability of the platelet fibrinogen receptor, the glycoprotein (GP) IIb-IIIa complex. This study was performed in order to determine the effects of intracellular calcium chelation on human platelet functions, on the expression of the fibrinogen receptor and on the stability of the GP IIb-IIIa complex. Intracellular Ca2+ of intact human platelets was extensively chelated by incorporation of high amounts (14-50 mmol/L) of the specific Ca2+ chelator quin2 after incubation of platelets with its lipophilic acetomethoxylester form (quin2-AM). We have investigated the effects of intracellular Ca2+ chelation with quin2 on platelet aggregation and fibrinogen binding induced by ADP and human alpha-thrombin and on the stability of the GP IIb-IIIa complex studied by crossed immunoelectrophoresis of Triton X-100 platelet lysates. The results were compared with control experiments performed with intact platelets treated with the impermeant Ca2+ chelator quin2 and with EDTA or EGTA. This study shows that high intracellular concentration of quin2 inhibits human platelet aggregation and fibrinogen binding but does not induce the dissociation of the GP IIb-IIIa complex. This study adds evidence for the role of external Ca2+ to maintain the integrity of a non-dissociated GP IIb-IIIa complex and suggests that intracellular Ca2+ is not involved in the stabilization of the GP IIb-IIIa complex.
Adenosine Diphosphate↗
Platelet activation revealed by reduced serotonin content in various left ventricular hypertrophic states.
The study of platelet function in thirty-one patients with left ventricular hypertrophy of various origins (9 cases of hypertensive cardiomyopathy, 11 of hypertrophic obstructive cardiomyopathy and 11 of aortic stenosis) revealed low serotonin content of platelets on the patients with left ventricular tract obstruction but normal levels in the hypertensive cardiomyopathy group. This is attributed to platelet activation induced by important flow disturbances related to the hemodynamic conditions.
Aortic Valve Stenosis↗
[Current view on non-Hodgkin lymphomas. Origin and evolution in relation to cytogenetic-histologic correlations].
Recent advances in immunology, cytogenetics and molecular genetics has allowed for a better understanding of the origin and evolution of non Hodgkin lymphoma (NHL). Over the last decade a number of recurrent chromosome aberrations has been disclosed and some correlations with well defined histologic subsets of B-cell NHL has been established. Five important cytogenetic-histologic associations has been documented, well defined by combined cytologic, immunologic and genetic investigations: t(14;18) (q32;q21) and NHL of follicle centre cell origin, frequently with follicular histologic pattern; t(8;14) (q24;q32) and Burkitt's lymphoma, Burkitt-like lymphoma or the equivalent small non-cleaved cell category of the "working formulation system"; t(3;22) (q27;q11) and diffuse large cell lymphoma; t(11;14) (q13;q32) and mantle zone lymphoma; trisomy 12 and chronic lymphocytic leukemia and well-differentiated small lymphocytic lymphoma. Molecular genetic studies elucidated some mechanisms operating during the normal lymphocyte differentiation which may be held responsible for the illegitimate recombination between the immunoglobulin genes and some oncogenes normally located on other chromosome regions. It has thus been demonstrated that the early events leading to neoplastic transformation in B-cell neoplasias occur in immature lymphocyte precursors in the bone marrow during the assembly of the immunoglobulin heavy chain gene. According to some recent studies chromosome changes may have prognostic value in B-cell NHL and chronic lymphocytic leukemia and may be employed in clinical practice in the construction of proportional hazard models in several histologic subsets of NHL.
Humans↗
Normal ADP-induced aggregation and absence of dissociation of the membrane GP IIb-IIIa complex of intact rat platelets pretreated with EDTA.
ADP-induced platelet aggregation requires the presence of external calcium and fibrinogen. When human platelets are incubated for 30 min at 37 degrees C with 5 mM EDTA and then resuspended in a calcium containing medium, they lose their ability to bind fibrinogen and to aggregate in response to ADP stimulation. Under these conditions, the effect of EDTA is irreversible and accompanied by dissociation of the glycoprotein (GP) IIb-IIIa complex into its free subunits, GP IIb and GP IIIa. We studied the effect of incubation of intact rat platelets with 5 mM EDTA at 37 degrees C from 30 to 120 min. EDTA treated rat platelets showed normal aggregation in response to 5 microM ADP in the presence of added purified rat fibrinogen and bound 125I-labeled rat fibrinogen at the same rate and magnitude after stimulation with 5 microM ADP as untreated platelets. Control and EDTA treated rat platelets, labeled or not with 125I and solubilized in Triton X-100, had a similar pattern of immunoprecipitates after crossed immunoelectrophoresis (CIE) analysis. The rat GP IIb-IIIa arc was located by incorporation of an 125I-labeled polyclonal anti-human GP IIb-IIIa antibody. In contrast, in experiments using rat platelet lysates, we demonstrated that the rat GP IIb-IIIa is a Ca(2+)-dependent heterodimer as it was dissociated by EDTA. Using SDS-PAGE and two-dimensional SDS-PAGE, the rat GP IIb-IIIa complex was found to have characteristics similar to the human complex with the exception that the light chain of the rat GP IIb was undetectable after 125I surface labeling.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine Diphosphate↗
cDNA cloning and expression of platelet p24/CD9. Evidence for a new family of multiple membrane-spanning proteins.
This study was designed to clone, sequence, and express the full-length cDNA for the human platelet p24/CD9 antigen. A 1.3-kilobase cDNA clone was identified that has an open reading frame encoding a mature protein of 228 amino acids (approximately 25,400 Da) containing 10 cysteine residues and four putative transmembrane domains. The identity of the clone was confirmed by: (i) its predicted size, (ii) identity to four peptide sequences from the isolated protein including the NH2 terminus, and (iii) expression of the isolated clone in Xenopus oocytes and Chinese hamster ovary cells. p24/CD9 has sequence identity (24-34%) to four other cell-surface proteins: ME491, a melanoma antigen; CO-029, a carcinoma antigen; CD37, a leukocyte antigen; and SM23, an antigen of the parasitic helminth Schistosoma mansoni. The five proteins have a similar number of amino acids and are characterized by the presence of four putative transmembrane domains. These data indicate the presence of a new family of surface antigens that may function in cellular activation and differentiation.
Amino Acid Sequence↗
Eosinophilic granuloma of the bone in Hand-Schüller-Christian disease: extensive in vivo eosinophil degranulation and subsequent binding of released eosinophil peroxidase (EPO) to other inflammatory cells.
The eosinophils from bone granuloma, bone marrow, and peripheral blood of a patient with Hand-Schüller-Christian disease (HSCD) were studied by electron microscopy and cytochemistry. Impressive eosinophil degranulation was observed. Extracellular release of eosinophil peroxidase (EPO) and EPO binding to surrounding cells were seen in the granuloma and bone marrow. Cells with peroxidase-positive plasma membrane were also observed in peripheral blood. The pattern of eosinophil degranulation showed quite different features from those described so far. In the granuloma, the process begins with intracytoplasmic release of the granule matrix content, as revealed by both extensive extragranular accumulation of EPO and progressive decrease of the matrix electron density. Core dissolution follows thereafter, leading to complete disappearance of the granules. At the end of the process, the cells show rupture of the plasma membrane and release of their content into the surrounding environment. This pattern of secretion was also observed in blood and marrow eosinophils of the patient. In view of the previously reported findings that EPO binding to inflammatory cells influences their functions, EPO release and binding to surrounding cells in HSCD may play a role in the evolution of the inflammatory lesion in the disease.
Bone Diseases↗
Cytochemically unreactive neutrophils from subjects with myeloperoxidase (MPO) deficiency show a complex pattern of immunoreactivity with anti-MPO monoclonal antibodies: a flow cytometric and immunocytochemical study.
Neutrophil granulocytes from 12 subjects with primary myeloperoxidase (MPO) deficiency (six totally deficient) and 16 patients with secondary partial MPO deficiency were tested using two different anti-MPO antibodies, in combination with either a flow-cytometric technique or an immunoalkaline phosphatase staining method. Results demonstrated three different cytofluorimetric patterns of immunoreactivity with the MPO protein: (a) a bright MPO antigenic expression, typical of patients with secondary MPO deficiency (comparable to that observed in the control group); (b) a medium MPO antigenic expression, typical of subjects with primary partial MPO deficiency; and (c) a dim MPO antigenic expression, characteristic of individuals with hereditary total MPO deficiency. No significant differences in granulocyte MPO reactivity were demonstrated for the two antibodies. Furthermore, in two individuals with complete primary enzyme deficiency, the single histogram analysis of MPO fluorescence determined by flow cytometry seemed to show that only 38% (case 1) and 44% (case 2) of neutrophils were reactive with the anti-MPO antibodies: the use of multiple histogram analysis in combination with Kolmogorov-Smirnov statistics allowed us to demonstrated that all the cells express a low density of MPO antigen. These data were more or less confirmed by the APAAP labeling method, which showed a reduced straining only in subjects with primary deficiency, while all patients with secondary deficiency had scores similar to those observed in controls (healthy subjects). Compared with the immunoenzymatic technique, the flow-cytometric procedure showed a higher sensitivity to MPO, being able to estimate even minor decreases in neutrophil MPO antigenic expression, as previously postulated by other authors. This work suggests that patients with primary MPO deficiency have different amounts of MPO antigens in the neutrophil granulocytes, and the levels of MPO fluorescence seem to decline concurrently with the enzyme activity, thereby suggesting the presence of a diminished MPO production. In contrast, the normal antigenic reactivity of neutrophils from patients with acquired MPO deficiency indicates the presence of a functionally inactive form of the enzyme.
Antibodies, Monoclonal↗
Evaluation of CR1 expression in neutrophils from chronic myeloid leukaemia: relationship between prognosis and cellular activity.
The expression of the complement receptor CR1 has been evaluated using an immunoalkaline phosphatase staining method on peripheral blood neutrophils and granulocyte precursors from 22 patients with chronic myeloid leukaemia (CML) and 15 healthy subjects. The immunocytochemical labelling pattern of CR1 was evaluated semiquantitatively on cell smears using three different anti-CR1 monoclonal antibodies. The scoring method showed that seven patients with CML had a marked reduction in CR1 expression which did not change with in vitro stimulation of neutrophils with phorbol-myristate-acetate (PMA) whereas control cells responded to PMA, increasing the receptor level two-fold. In addition, functional analysis of neutrophils with low CR1 expression from CML patients showed a very low cytolytic activity against K562 tumour target, suggesting a relationship between the cellular content of CR1 and neutrophil tumouricidal activity. The involvement of CR1 in neutrophil-mediated lysis is consistent with complete lack of tumour toxicity following receptor neutralization by anti-CR1 monoclonal antibodies. Interferon therapy improved CR1 expression and the cytolytic response of neutrophils in three out of five CML patients with a moderately low CR1 score. CML patients non-responding to interferon therapy and those with a very low CR1 score, independent of the clinical stage, progressed more rapidly into the advanced clinical stage and blastic crisis.
Complement C3b↗
[Cytofluorometric study of myeloperoxidase (MPO) expression in neutrophilic granulocytes of subjects with primary or secondary MPO deficiency: analysis of the histographic antigen distribution using the Kolmogorov-Smirnov mathematical model].
Neutrophil granulocytes from 12 subjects with primitive myeloperoxidase (MPO) deficiency (6 totally deficient) and 16 patients with secondary partial MPO deficiency were tested using two different anti-MPO monoclonal antibodies (MoAbs), in combination with a flow cytometer. Results demonstrated three different patterns of immunoreactivity with the MPO protein:i) a bright MPO antigenic expression, typical of patients with secondary MPO deficiency (comparable with that observed in the control group); ii) a medium MPO antigenic expression, typical of subjects with hereditary partial MPO deficiency; and iii) a dim MPO antigenic expression, characteristic of individuals with hereditary total MPO deficiency. No significant differences in granulocyte MPO reactivity were demonstrated for the two MoAbs. Furthermore, in two individuals with complete primitive deficiency, the single histogram analysis of MPO fluorescence seemed to show that only 38% (case 1) and 44% (case 2) of neutrophil were reactive with the MoAbs anti-MPO: the use of multiple histogram analysis in combination with Kolmogorov-Smirnov statistics allowed us to demonstrate that all the cells express a low density of MPO antigen. These data suggest that patients with primary MPO deficiency have different amount of MPO antigens in the neutrophils, and the levels of MPO fluorescence seem to decline concurrently with enzyme activity, thereby suggesting the presence of a diminished MPO production. On the contrary, in most cases of acquired MPO deficit, the reduced cytochemical activity contrasts with normal antigenic reactivity: this might be the result of the presence of an inactive enzyme.
Antibodies, Monoclonal↗
Characterization of the human platelet glycoprotein IIIa gene. Comparison with the fibronectin receptor beta-subunit gene.
This study was designed to determine the structure of the gene for glycoprotein (GP) GPIIIa, the beta-subunit of the platelet membrane GPIIb-IIIa complex. The complexity of the gene was determined after Southern analysis of human chromosomal DNA. Overlapping genomic clones were isolated from cosmid and phage lambda libraries that contained the entire coding unit of the human gene for the mature GPIIIa protein. The genomic clones spanned approximately 60 kilobase pairs of human DNA sequence. The exon containing segments of the clones was mapped and the exons, including the exonintron junctions, were sequenced. The GPIIIa protein is divided into 14 exons ranging in size from 87 to 430 nucleotides separated by introns, which were 0.3 to 9 kilobase pairs in size. The 3' exon was larger than 1700 nucleotides and contained the 3'-untranslated region. Several structural domains of the GPIIIa protein were contained within individual exons. These included (i) the transmembrane spanning segment, (ii) the cytoplasmic region containing the potential phosphorylation sites, and (iii) the six domains in the NH2-terminal half of GPIIIa that are highly conserved between two other integrin beta-subunits. In contrast, other domains such as the four cysteine-rich repeats were interrupted by introns. Genomic clones for the beta-subunit of the fibronectin receptor (beta 1) were also isolated, partially mapped, and sequenced. Of the eight splice sites identified in beta 1, six occurred at the same amino acid residue in GPIIIa. These results provide genetic evidence that GPIIIa and beta 1 have a common evolutionary origin within the integrin family.
Amino Acid Sequence↗
The thienopyridine PCR 4099 selectively inhibits ADP-induced platelet aggregation and fibrinogen binding without modifying the membrane glycoprotein IIb-IIIa complex in rat and in man.
The thienopyridines, ticlopidine and PCR 4099, inhibit ex vivo aggregation in response to ADP and other agonists. It has been shown that ticlopidine induces a functional defect in the binding of fibrinogen to its platelet membrane receptor. We have studied the effects on platelet functions of PCR 4099 in rat and in man. The aim of the study was to check the possibility of a direct modification of the fibrinogen binding site on the GP IIb-IIIa complex. Washed platelet suspensions were used for aggregation and fibrinogen binding studies. Platelet lysates were submitted to SDS-polyacrylamide gel electrophoresis, crossed immunoelectrophoresis and immunoprecipitation. We found that administration of PCR 4099 inhibited selectively and irreversibly ADP-induced aggregation. Although the effect of ADP on aggregation was blocked, PCR 4099 did not modify ADP-induced shape change. Only the effects of low concentrations of thrombin on platelet aggregation were inhibited. Fibrinogen binding was dramatically inhibited in rat and in man when platelets were stimulated with ADP and low concentrations of thrombin. At high concentration of thrombin there still remained a part of fibrinogen binding inhibition although aggregation was not impaired. Electrophoretic and immunoelectrophoretic studies showed no difference before and after treatment by PCR 4099. In particular, the GP IIb-IIIa-complex was not dissociated, its electrophoretic mobility was not changed and three monoclonal anticomplex antibodies recognized it in the same manner before and after treatment. We conclude that PCR 4099 selectively inhibits the ADP aggregation pathway and that the inhibition of fibrinogen binding is probably not due to a direct modification of the GP IIb-IIIa complex.
Adenosine Diphosphate↗
Clinical pharmacology of predisintegrated ibuprofen 800 mg tablets: an endoscopic and pharmacokinetic study.
Thirty-five healthy adults were randomized to receive either: (1) ibuprofen 800 mg tablets; (2) ibuprofen 800 mg aqueous suspension; (3) ibuprofen 800 mg orange juice suspension; or (3) 325 mg aspirin tablets. All treatments were tid for 7 days. Pharmacokinetic sampling was conducted on days 1, 4 and 8. Gastroduodenoscopy was performed on days 1 and 8. Side effects and safety laboratory tests were monitored throughout the study. On day 8 the aspirin group showed significantly more gastric irritation than all of the ibuprofen groups (P less than .005). Both ibuprofen suspension groups showed more gastric irritation than the ibuprofen tablet group (P less than .1). The duodenal scores did not differ among the treatment groups. The aspirin group experienced a higher rate of tinnitus and abdominal pain. The rate and extent of absorption of the ibuprofen suspensions were significantly less than that of the tablets. These data suggest that the taking of ibuprofen as an extemporaneous suspension is therapeutically inferior to ibuprofen tablets and therefore should be discouraged.
Adult↗
Phase II cooperative study with a new alkylating drug, PTT-119, in the treatment of non-Hodgkin's lymphomas.
In a phase II cooperative study involving eleven Italian haematological units, the efficacy and toxicity of a new alkylating compound, PTT-119, was evaluated in 53 patients with non-Hodgkin's lymphoma (NHL). Forty-five of the patients had been previously treated with various regimens of chemotherapy, the remaining eight were at the onset of the disease. PTT-119 was scheduled at 3.0 mg/kg every three weeks for a minimum of three administrations. Seven patients achieved a complete remission (CR), 19 a partial remission (PR); the overall response rate was 49%. The median duration of response was 6 months. Most frequent adverse effects were alopecia, nausea and vomiting and phlebitis due to the drug infusion. Myelosuppression was severe only in patients with bone marrow involvement or who were heavily pretreated. No liver, cardiac or renal toxicity was recorded. These data indicate that PTT-119 is an effective drug in the treatment of NHL; the matter of its non-cross-resistance with other alkylating compounds warrants further studies.
Adult↗
Neutrophil defect associated with hairy cell leukemia.
We have investigated the motility, superoxide anion production and tumor cell lysis of neutrophils from five patients affected by hairy cell leukemia. Random locomotion and chemotaxis towards denaturated casein and activated serum was normal as well as the superoxide production by opsonized zymosan. In contrast, chemotaxis and superoxide generation induced by FMLP and TPA were markedly reduced. The low responsiveness of neutrophils to TPA was also observed by evaluating cell lysis, against either non-immunized K562 target cells or antibody-coated tumor targets. In hairy cell leukemia neutrophils showed a selective reduced response to TPA and FMLP that, directly or indirectly, activate PKC, suggesting an impairment in the system of signal transduction.
Cell Movement↗
[Spontaneous esophageal rupture or Boerhaave's syndrome. Presentation of a case].
A case of spontaneous oesophageal rupture or Boerhaave syndrome is described. The absence of the typical initial vomiting together with a clinical picture that successively indicated repeated myocardial infarction, pancreatitis and pulmonary abscess delayed diagnosis by 4 days, after which emergency thoracotomy, performed on the identification of extravisceral overflow by contrast radiography using a water-soluble medium, revealed necrotic inflammation of the oesophagus, mediastinum and left lung that was so severe that only thoracic drainage was possible. After an initial improvement the patient died of septic shock on the 16th postoperative day.
Aged↗
Lymphocytes treated with natural alfa-interferon produce a chemotactic factor for human neutrophils.
Lymphocytes stimulated with alfa-interferon released a chemotactic factor for neutrophils. The process was not inhibited by cycloheximide, whereas mepacrine completely inhibited release of the chemotactic activity. The chemotactic factor was resistant to storage, heat treatment and proteolysis. Recombinant alfa-interferon did not stimulate lymphocytes to release a neutrophil chemotactic factor.
Cells, Cultured↗