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M Schena

Publications and source records attributed to M Schena.

61 records · Page 4Linked to original sources

Comparative analysis of normal and malignant CD5+ B lymphocytes.

The T-cell related CD5 molecule is expressed by the major B cell population which forms primary follicles in fetal lymph nodes and spleen and circulates in cord blood but decreases to a numerically minor proportion (5-10% of all B cells) in adults [1, 3-5, 8, 9, 12, 14, 16]. The CD5 molecule is also expressed by the monoclonal B cells of B-chronic lymphocytic leukemia (B-CLL: reviewed in [5]). Even if there is no proof that CD5+ B cells are the target of the transforming events which lead to B-CLL, they are regarded as the normal counterpart of B-CLL. Therefore, the aim of the present work was the analysis of the phenotype, the cell cycle control and the cytoskeleton organization of normal CD5+ B lymphocytes in comparison with the data obtained on malignant CD5+ cells from B-CLL patients.

Antigens, Differentiation, B-Lymphocyte↗

Acute administration of melatonin at two opposite circadian stages does not change responses to gonadotropin releasing hormone, thyrotropin releasing hormone and ACTH in healthy adult males.

We evaluated the effect of a single oral administration of 100 mg melatonin (MT) vs placebo (PL) on the pituitary release of LH, FSH, TSH and prolactin (PRL) after GnRH + TRH and on the adrenocortical release of cortisol, aldosterone and progesterone after ACTH in healthy adult males. We carried out a double blind study in 6 volunteers in winter, at two opposite stages of the circadian cycle: 08:00 and 20:00 h. Injection of GnRH (100 micrograms), TRH (200 micrograms) and ACTH (10 micrograms of the synthetic ACTH 1-17 analogue, Alsactide) was performed one h after MT or PL ingestion. Plasma MT levels were 200-4,000-fold higher after MT than PL thus confirming the effective gastrointestinal absorption of the pineal hormone. The hormonal patterns were superimposable after MT and PL. A higher response of PRL, FSH and cortisol was observed in the evening vs morning protocols independently of previous MT or PL. Our data demonstrate that the acute oral administration of a pharmacological dose of MT at two opposite circadian stages is ineffective to change a variety of pituitary and adrenocortical responses in human male subjects. The circadian chronosusceptibility of pituitary and adrenocortical cells to specific stimuli deserves interest to future investigation.

Adrenocorticotropic Hormone↗

C3b receptors mediate the growth factor-induced proliferation of malignant B-chronic lymphocytic leukemia lymphocytes.

We have investigated the function of C3b receptor (CR1) in the malignant lymphocytes of B-chronic lymphocytic leukemia (B-CLL) mimicking the physiological ligand C3b with the anti-CR1 monoclonal antibody CB04 covalently linked to Sepharose CL-4B (CB04-S). The binding of insolubilized CB04-S to CR1 gave a progression signal to B-CLL cells which became B cell growth factor (BCGF)-responsive. The cells of 13 of 14 cases treated with CB04-S showed an active time-dependent proliferation when BCGF was added to the culture. After 72 hr of exposure to BCGF, the growth fraction evaluated with the Ki67 monoclonal antibody was 23.4 +/- 8.9 and the proportion of cells in S phase assessed by the bromodeoxyuridine incorporation technique was 18.6 +/- 8.5%. The proper sequence of CB04-S followed by BCGF was also important since the proliferation was halved when the sequence was reversed or the two signals were delivered concomitantly. CB04-S and BCGF alone failed to induce any significant proliferation; the percentage of cycling cells was less than 1% overlapping that of control culture cells. On the contrary, the proliferation of normal tonsil B cells was triggered both by CB04-S and by BCGF used as single agents (bromodeoxyuridine+ cells 12.7 +/- 5.1% and 20.0 +/- 7.3, respectively). Together these data indicate that malignant B-CLL cells need a sequential two-step signal based upon CR1 binding in order to be activated in vitro. This is a major difference with normal tonsil B lymphocytes whose proliferation is triggered both by CB04-S and by BCGF used as single agents.

Aged↗

Compensatory regulation in metabolic pathways--responses to increases and decreases in citrate synthase levels.

The level of citrate synthase was varied in Escherichia coli by recombinant DNA methods to elucidate regulatory interactions between the individual steps of the citric acid cycle. The effects of overproduction and underproduction of citrate synthase were assessed by measuring metabolite levels, rates of carbon flow, the phosphorylation state of isocitrate dehydrogenase, and the growth rate of the culture. This analysis revealed that the levels of citrate synthase and isocitrate dehydrogenase activity are co-ordinated for efficient growth on acetate. When citrate synthase was overproduced the isocitrate dehydrogenase reaction became rate limiting and prevented large increases in the flux through the citric acid cycle. Furthermore, changes in the level of citrate synthase were found to modulate the phosphorylation state of isocitrate dehydrogenase which regulates the distribution of carbon flow between the citric acid cycle and the glycoxylate shunt. These adjustments allowed the organism to maintain a relatively constant metabolic state despite changes in the level of a central metabolic enzyme. The interplay between citrate synthase and isocitrate dehydrogenase illustrates how living systems can compensate for variations in their internal environment.

Acetates↗

[Alpha 1-antitrypsin as a tumor marker].

In this work we intended: a) to confirm the correlation between the increase of serum levels of alpha 1-antitrypsin (ATT) and neoplastic disease; b) to verify in what tumoural diseases the increase of ATT has a specific significance. Therefore we have examined 164 patients: 60 represented the control group and 104 were suffering from neoplastic diseases. We have subdivided the nest group according to histological type and tumour location. The result of this work has demonstrated that the increase of ATT is really determined by the existence of neoplastic disease, more than histological type or location of cancer. The AAT represents a diagnostic index of neoplastic diseases, highly sensitive but little specific.

Carcinoma↗

In situ hybridization and immunocytochemistry of alpha1-adrenoceptors in human peripheral blood lymphocytes.

1 alpha1-Adrenoceptor subtypes were investigated in cytospin centrifuged preparations of human peripheral blood lymphocytes by in situ hybridization and immunocytochemistry. 2 In situ hybridization cytochemistry revealed alpha1A-, alpha1B-, and alpha1D-receptor mRNA in human peripheral blood lymphocytes. Lymphocytes hybridized for alpha1A receptor subtype represented approximately 30% of total lymphocytes, those hybridized for alpha1Beta- and alpha1D-receptor subtypes averaged 42 and 25% of total lymphocytes, respectively. 3 Cytospin centrifuged lymphocytes exposed to anti-alpha1A-, alpha1Beta- or alpha1D-receptor protein antibodies, developed specific immunostaining. Approximately 27% of total lymphocytes were immunoreactive for alpha1A-receptor protein, 40% displayed alpha1B-receptor protein immunoreactivity and 22% alpha1D-receptor protein immunoreactivity. Analysis of percentages as well as of lymphocyte morphology of in situ hybridized and immunolabelled lymphocytes suggests the co-expression of mRNA receptor signal and protein receptor immunostaining in the same lymphocyte. 4 The demonstration of both alpha1-adrenoceptor mRNA and receptor protein subtypes suggests that alpha1-adrenoceptors may have a role in regulating lymphocyte function. 5 The possibility of demonstrating receptor protein immunoreactivity in a small amount of blood, such as that required for preparing cytospin-centrifuged lymphocytes, may stimulate research to evaluate the role of these receptors in lymphocytes and to establish if assessment of lymphocyte alpha1-adrenoceptors may represent a marker of their status in health and disease.

Adult↗