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Biomedical subjects

L M Larocca

Publications and source records attributed to L M Larocca.

106 records · Page 6Linked to original sources

T lymphocyte subsets and platelet-associated IgG in idiopathic thrombocytopenic purpura: effect of splenectomy.

The modifications of cell-mediated immunity in idiopathic thrombocytopenic purpura (ITP) were investigated using the technique of Moretta et al. [J. exp. Med. 151: 969-974, 1980] to study T lymphocyte subsets in 35 ITP subjects at various clinical stages. In all these patients, platelet-associated IgG (PAIgG) were measured by a complement lysis inhibition technique. Untreated ITP patients did not show significant modifications of T lymphocyte subsets. Patients with thrombocytopenia not responsive to corticoids or splenectomy and increased PAIgG levels showed significant reduction of Fc-gamma-bearing T lymphocytes (T-gamma). Patients 'cured' by splenectomy (12 out of 17) showed a normal PAIgG level, a marked increase of T-gamma cells and a reduction of T-mu cells; patients 'not cured' by splenectomy showed an increased PAIgG level and a reduction of T-gamma cells. An increase of PAIgG levels and a reduction of T-gamma cells were found in 2 splenectomized patients after relapse. An association between chronic nonresponsive ITP and decrease of T-gamma cells was established.

Adolescent↗

Distribution of circulating mononuclear cells in short-term PUVA-treated psoriatic patients and healthy subjects.

Peripheral blood mononuclear cells (PBMC), as defined by monoclonal antibodies (OKT3, OKT4, OKT8, OK 1, Leu 7, Leu 11b) were determined in 10 psoriatic patients and in 10 healthy subjects before and after administration of short-term PUVA therapy. A comparison of the mean baseline percentages of the two groups showed a statistically significant increase in Leu 7+ cells (p less than 0.001) as well as a slight increase in OKM1 and OKT8 positive cells in the psoriatic subjects. After 21 exposures, these subsets showed a reduction towards control values, while a significant increase in OKT3 and OKT4 positive cells (p less than 0.01) could be observed only in the control group. These results indicate that short-term PUVA therapy is associated with changes in PBMC subpopulations. This modification, however, does not necessarily imply a disturbance of immune system function, including natural killer activity.

Adult↗

Expression of 20 alpha-hydroxysteroid dehydrogenase activity in human lymphoid and non lymphoid cells.

Expression of 20-alpha-hydroxysteroid dehydrogenase (20 alpha-SDH), a putative T cell marker in the murine system, has been examined in human haematopoietic cells. Higher levels of enzymatic activity were expressed by human peripheral blood mononuclear cells (PBMC) in comparison with thymocytes. When PBMC were fractionated into T and non T cell subsets, the greatest values of 20 alpha-SDH activity were associated with the non T cell population. Cells from bone marrow exhibited lower levels of 20 alpha-SDH than PBMC and thymocytes. Both myeloid and lymphoid leukaemic cells expressed significant 20 alpha-SDH activity. In addition our data in U-937 and CM-S human cell lines indicate that cells belonging to the myelomonocytic precursor compartment constitutively expressed 20 alpha-SDH activity. Furthermore, this activity was less expressed when these cells were induced to monocyte-macrophage differentiation. In conclusion, our data in the human system indicate that 20 alpha-SDH should not be viewed as a lymphoid lineage-restricted marker enzyme.

20-Hydroxysteroid Dehydrogenases↗

Estrogen binding sites in peripheral blood mononuclear cells and thymocytes from 2 myasthenia gravis patients.

In the present investigation the estrogen binding capacity of peripheral blood mononuclear cells (PBMC) and thymocytes from 2 young female Myasthenia Gravis (MG) patients has been studied. We found high levels of estrogen binding sites in both pre-thymectomy PBMC and lymphoid cells from the hyperplastic thymuses of the MG patients. A sucrose density gradient analysis revealed that the estrogen was binding to macromolecular species similar to those characterized in cytosols from classical estrogen target organs. A post-thymectomy time-dependent decrease of the estrogen binding capacity was also observed in PBMC, reaching levels similar to that of sex- and age-matched controls.

Adolescent↗

Transient deficiency of peripheral blood accessory cells in supporting T cell mitogenesis in patients suffering from chronic idiopathic thrombocytopenic purpura after intravenous gammaglobulin treatment.

Mitogenic response of blood lymphocytes to phytohemagglutinin (PHA) and to OKT3 monoclonal antibodies was investigated in 7 patients suffering from chronic idiopathic thrombocytopenic purpura (ITP) before, during and after high-dose intravenous (i.v.) immunogammaglobulin (IgG) infusion. The platelet count rose above the pre-treatment values during infusion therapy in all patients but one. Five out of seven patients presented elevated platelet-associated IgG (PA-IgG) levels at the time of the first infusion; four of these showed an increase in platelet count and a transient reduction or normalization of PA-IgG after IgG infusion. Five out of seven patients showed an impairment of T lymphocyte mitogenic response to PHA and OKT3 before therapy. All patients responded to IgG therapy with a transient deficiency of FcR mediated monocytes (Mo) in supporting T cell mitogenesis induced by both mitogens during and after IgG infusion. This reduced cooperative capability of Mo disappeared at various times after the end of therapy (range 3-12 days). The transient alteration of Mo function, possibly due to a modification in the surface number or in the affinity of Fc-receptors, can explain in part, the increase in platelet count during and after IgSRK infusion.

Antibodies, Monoclonal↗

T3 expression by human thymocytes in culture.

By panning procedures employing T6 and T3 monoclonal antibody, human thymocytes were fractionated into two subpopulations depleted of T6- or T3-positive (T6+, T3+) cells. Unfractionated thymocytes and T6- and T3-depleted subpopulations were separately cultured for 48 h in RPMI 1640 medium with 10% FCS or in HB 101 serum-free medium. Determining the phenotype of unfractionated thymocytes at various time intervals, a time-dependent increase of T3+ cells was observed. An inverse relationship was found between the percentage of T3+ cells and the T6 and peanut agglutinin (PNA) reactive thymocytes. When the surface antigen expression in the T3-depleted population (greater than 95% T6+ and PNA+ cells) was analysed, a strong increase of T3+ cells and a complementary reduction of T6+ and PNA+ cells was evidenced. During that time the surface phenotype of the T6-depleted population (greater than 80% T3+ cells) showed the same trend of differentiation, as the other thymocyte preparations. These results indicate that a conspicuous fraction of human thymocytes and particularly of those characterized by a cortical phenotype (PNA+ and T6+ cells), are able to express mature T-cell antigens when cultured in vitro in the absence of the thymic microenvironment influence. However, the in vitro acquisition of a mature phenotype is not accompanied by a parallel achievement of the capacity to respond to mitogens such as PHA or T3 monoclonal antibody.

Antibodies, Monoclonal↗

Ultrastructural analysis of peripheral blood mononuclear cells in renal allograft recipients.

Renal transplanted patients receiving immunosuppressive therapy with glucocorticoids (GC) and azathioprine show in the peripheral blood numerous large mononuclear cells. The origin and the lineage of these cells was not clearly established. In the present study we investigated the surface phenotype and the ultrastructural characteristics of this subset constituted by large mononuclear cells. From peripheral blood mononuclear cells (PBL) of allograft recipients, a cell preparation exhaustively depleted of the relatively numerous monocytes was obtained. At ultrastructural examination two main cellular populations were distinguished: the predominant one (congruent to 85%) was constituted by cells with lymphoid morphology while the other (congruent to 15%) showed myeloid appearance. The large lymphoid cells, T4 or T8 positive, did not express Ia molecules on the surface and were morphologically suggestive of cells in an intermediate stage of the cell cycle between resting and activated lymphocytes. The myeloid population was constituted by promyelocytes, myelocytes and metamyelocytes. Promyelocytes and myelocytes capable of cell division are responsible for the increase of 3H-thymidine incorporation observed in transplanted patient PBL. In conclusion our data suggest that in allograft recipients the immunosuppressive therapy with GC and azathioprine may inhibit the lymphocyte blast transformation and can influence the release of immature myeloid cells responsible for the PBL increased 3H-thymidine incorporation.

Antibodies, Monoclonal↗

Delayed allergy to aminopenicillins: clinical and immunological findings.

Aminopenicillins are the most used beta-lactam antibiotics. Morbilliform or maculopapular rashes are rather frequent during therapy with aminopenicillins. The pathogenesis of these reactions is often due to a cell-mediated allergy. The aim of this work is to characterize patients with cell-mediated allergy to aminopenicillins and to identify alternative beta-lactam drugs that can be safely administered to these patients. We studied 27 subjects affected by cell-mediated allergy to aminopenicillins. The diagnosis was made on the basis of positivity of patch tests with aminopenicillins. These patients then underwent an allergological evaluation (skin and patch tests, oral and/or intramuscular challenge tests) with a wide spectrum of beta-lactam antibiotics. Our work highlights the following main characteristics of cell-mediated allergy to aminopenicillins: time elapsing between drug administration and onset of symptoms of about 2 days; the maculopapular rash and delayed appearance of urticaria/angioedema were the most typical symptoms (82.8 percent of cases); a cross-reactivity with aminocephalosporins is usually absent, or it is limited to cephalexin (in our study, in fact, just 3 out of 20 patients challenged with cephalexin showed a positive oral challenge test); all the beta-lactams, other than aminopenicillins, are well tolerated. Patch tests represent a specific diagnostic tool with a good predictive value of identifying alternative drugs that can be safely administered to patients with beta-lactam allergy. Our patients could tolerate other beta-lactam drugs after a complete allergological evaluation. On the basis of our study, cell-mediated allergy to aminopenicillins should be considered a well-defined nosologic entity.

Administration, Oral↗

Synchronous gastric adenocarcinoma and MALT lymphoma in a patient with H. pylori infection. Could the two neoplasms share a common pathogenesis?

Low-grade primary MALT (mucosa-associated lymphoid tissue) lymphoma of the stomach is a neoplasm with an indolent course and a good prognosis. Patients with this type of neoplasm seem to have a higher risk for other neoplasms. Of interest is the association of gastric MALT lymphoma with gastric adenocarcinoma of intestinal type. We report the case of a patient, with a history of H. pylori-related gastritis, in whom a diagnosis of synchronous gastric adenocarcinoma of intestinal type and low-grade MALT lymphoma, occurring as collision tumors, was made. The stage procedures confirmed the presence of a locally advanced gastric tumor staged as T3 N1. The patient underwent two cycles of neoadjuvant EEP (etoposide, epirubicin, cisplatin) chemotherapy. After 2 months, a R0 total gastrectomy with D2-lymphoadenectomy was successfully performed. The development of simultaneous primary gastric lymphoma and carcinoma is a rare event. The possible coexistence of both tumors should be kept in mind, especially in patients infected with H. pylori, since a possible etiopathogenetic role of this bacterium has been differently postulated for both disease.

Adenocarcinoma↗

Type II estrogen binding sites (EBS) in intracranial tumors.

Four meningiomas and six neuroepithelial tumors were assayed for the presence of estrogen receptors (ER), type II estrogen binding sites (EBS) and progesterone receptors (PgR). ER were detected in 7 out of 10 cases with levels ranging between 2.5 and 20.7 fmoles/mg of cytosolic protein. On the contrary, PgR were found in all samples (10 cases) and their levels ranged between 8.8 and 130.6 fmoles/mg of cytosolic protein. All tumor samples expressed appreciable amounts of type II EBS ranging between 452 and 2320 fmoles/mg of protein. Although the precise functional role of type II EBS is still unknown, their presence may reflect an hormonal sensitivity of these tumors.

Brain Neoplasms↗

[Visceral leishmaniasis in patients with AIDS. Description of 2 cases].

Cell-mediated immunity plays a pivotal role in the pathogenesis and in the recovery mechanisms of visceral leishmaniasis (V.L.). This disease, observed in two patients with AIDS, has peculiar anatomical and clinical characteristics and it is usually characterized by a severe clinical course. In addition, V.L. has been proposed to be included among the relevant infections for the case definition of AIDS. We describe two cases of V.L. occurred in association with AIDS. The most relevant characteristics of our cases are the followings: Diagnosis has been achieved by the identification of Leishmania donovani in the macrophages of the bone marrow in both the patients, and of the lymph node in one patient. The detection of anti-Leishmania antibodies was positive in one patients only. A significant defect of CD4+ cells was documented in both the patients. V.L. was associated in one patient with esophageal candidiasis, disseminated tuberculosis, P. carinii pneumonia; and in the other one with cerebral toxoplasmosis, pulmonary tuberculosis, esophageal candidiasis, Kaposi's sarcoma, CMV hepatitis. Specific chemotherapy has been partially or totally ineffective in both the patients. In fact, chemotherapy led to an apparent transient recovery in one patient, followed by a symptom-free period of more than one year. We think that V.L. has been the first infection occurred in this patients, beside of HIV infection. At the time of the first observation, the clinical conditions of this patient were satisfactory and there was only a slight alteration in cellular immunity. The detection of leishmania in bone marrow was coincident with the onset of fever, the development of a wasting syndrome and a dramatic decrease in cell-mediated immunity. A second cycle of specific treatment has been ineffective and the patient died. On the contrary, the second patient did not respond to the specific treatment and died. Two important anatomo-pathological characteristics were present in our cases: a) the presence of the parasite in several organs, namely bone marrow, spleen, liver. b) the absence of granulomatous lesions which indirectly indicates the defect in cell mediated immunity.

Acquired Immunodeficiency Syndrome↗

[Recent advances concerning etiopathogenesis of nasal polyposis].

The way nasal polyps arise and why they tend to recur is still unknown. Quite frequently they are found in association with asthma, rhinitis and ASA-intolerance, thus suggesting a multifactorial etiopathogenesis. The incidence of atopy in patients affected with nasal polyposis is quite low (16.8%). Recent studies stress the involvement of mast cell mediators due to various degranulating stimuli other than those mediated by IgE. The finding of the interleukin-2 receptor (IL2-R) on murine mast cells and on human peripheral blood basophils, together with the possibility of inducing basophil degranulation through IL2 stimulation, have led the authors to seek IL2R on human nasal polyp mast cells and to study subpopulations of nasal polyp lymphoid infiltrates. Nasal polyps obtained from 4 patients, admitted to the E.N.T. Department of the Catholic University of Rome in 1988, were snap frozen soon after their surgical removal through transmaxillary ethmoidectomy. In this study the following monoclonal antibodies (MoAb) were used: Leu-2a (CD8), Leu-3a/3b (CD4), Leu-4 (CD3), anti-HLA-DR and anti-IL2-R (CD25), OKM1 (CD11), OKB2 (CD24) and 1HT4-4H3 (CD 25). In no patient was there evidence of atopy, asthma or ASA-intolerance. Several mast cells (MC) were observed, chiefly in the connective axis and perivascular areas. These cells were characterized by a large number of cytoplasmatic monomorphic granules. The MC displayed the IL2-R and they were very often close to T-lymphocytes. T-cell subpopulations were predominantly composed of CD4-positive cells (about 75% of all lymphocytes) often associated in clusters and located both in the submucosa and in the connective axis. CD8-positive cells (10-15% of the lymphoid cells) were located most often just under the epithelium. They were hardly ever scattered within the CD4-positive cell clusters. Almost all T cells were activated, above all those surrounding the MC. These results would appear to suggest the presence of a cell-mediated immune response in nasal polyp pathogenesis where MC degranulation, determined by activated T-cell cytokines, plays an important role.

Adult↗