The development and validation of the Body Image Dimensional Assessment (BIDA).

AIM: To validate a silhouette-based scale, the Body Image Dimensional Assessment (BIDA), an instrument for the screening of body dissatisfaction in large samples. MATERIALS AND METHODS: Five-hundred ninety-two both gender non-clinical participants and 57 patients with eating disorders (ED) were administered the BIDA and the Body Dissatisfaction subscale of the Eating Disorder Inventory 2 (BD-EDI2). The BIDA consists of only 4 items to answer with reference to a series of four silhouettes not age- nor gender-related using a numeric scale that allows the quantification of the degree of Body Dissatisfaction, Sexual Body Dissatisfaction, Comparative Body Dissatisfaction and the calculation of the final Body Dissatisfaction Index (BDI). RESULTS AND CONCLUSIONS: The study has shown that the BIDA has good reliability and validity as well as high predictive capability at a threshold BDI≥30 (sensitivity = 83.3% and specificity = 92.1%). By virtue of the rapid timing of administration, the BIDA can be a useful screening instrument of body dissatisfaction in non clinical populations to detect people at risk for ED and a follow-up instrument in clinical setting.

RB2/p130 gene-enhanced expression down-regulates vascular endothelial growth factor expression and inhibits angiogenesis in vivo.

Angiogenesis is an essential step in the progression of tumor formation and development. The switch to an angiogenetic phenotype can occur as a distinct step before progression to a neoplastic phenotype and is linked to genetic changes such as mutations in key cell cycle regulatory genes. The pathogenesis of the angiogenetic phenotype may involve the inactivation of tumor suppressor genes such as the "guardian of the genome," p53, and the cyclin-dependent kinase inhibitor p16. Retinoblastoma family member RB2/p130 encodes a cell cycle regulatory protein and has been found mutated in different tumor types. Overexpression of RB2/p130 not only suppresses tumor formation in nude mice but also causes regression of established tumor grafts, suggesting that RB2/p130 may modulate the angiogenetic balance. We found that induction of RB2/p130 expression using a tetracycline-regulated gene expression system as well as retroviral and adenoviral-mediated gene delivery inhibited angiogenesis in vivo. This correlated with pRb2/p130-mediated down-regulation of vascular endothelial growth factor protein expression both in vitro and in vivo.

Nuclear matrix provides linkage sites for translocated NF-kappa B: morphological evidence.

In response to the binding of extracellular ligands to cell surface receptors, multiple transcription factors are activated in the cytoplasm and translocated into the nucleus where they exert positive or negative control over cellular genes. The human transcription factor NF-kappa B family regulates the expression of a large number of genes involved in the host defence mechanism. They are typically present in the cytoplasm bound to the inhibitory I kappa B proteins. The activation of NF-kappa B involves the signal-induced degradation of these proteins, allowing NF-kappa B to translocate to the nucleus. In this study, by multiparametric analysis, we recognise in RPMI-8402 DMSO-activated cells the intracellular movement of transcription factor NF-kappa B providing its definite intranuclear collocation. Intact cells, purified nuclei and nuclear matrix preparations after 4 h of treatment were processed for morphological and biochemical analyses. Light and electron microscope observations show, in untreated cells, the presence of NF-kappa B protein homogeneously retained in the cytoplasm. Treated cells display a massive presence of NF-kappa B at the nuclear level bound to the interchromatin region. Immunoblotting of the same specimens confirms the strong association of NF-kappa B with the nuclear scaffold. Taken together, the data presented in this manuscript support a model where DMSO treatment provokes the cleavage and translocation of NF-kappa B from the cytoplasm to the nucleus and, in particular, in the proteinaceous network of the nuclear matrix sustaining the active role of this subcellular structure on regulation of eukaryotic gene expression.

Conventional and new antidepressant drugs in the elderly.

Depression in the elderly is nowadays a predominant health care problem, mainly due to the progressive aging of the population. It results from psychosocial stress, polypathology, as well as some biochemical changes which occur in the aged brain and can lead to cognitive impairments, increased symptoms from medical illness, higher utilization of health care services and increased rates of suicide and nonsuicide mortality. Therefore, it is very important to make an early diagnosis and a suitable pharmacological treatment, not only for resolving the acute episode, but also for preventing relapse and enhancing the quality of life. Age-related changes in pharmacokinetics and in pharmacodynamics have to be kept into account before prescribing an antidepressant therapy in an old patient. In this paper some of the most important and tolerated drugs in the elderly are reviewed. Tricyclic antidepressants have to be used carefully for their important side effects. Nortriptyline, amytriptiline, clomipramine and desipramine as well, seem to be the best tolerated tricyclics in old people. Second generation antidepressants are preferred for the elderly and those patients with heart disease as they have milder side effects and are less toxic in overdose and include the so called atypicals, such as selective serotonin reuptake inhibitors, serotonin noradrenalene reuptake inhibitors and noradrenaline reuptake inhibitors. Monoamine oxidase (MAO) inhibitors are useful drugs in resistant forms of depression in which the above mentioned drugs have no efficacy; the last generation drugs (reversible MAO inhibitors), such as meclobemide, seem to be very successful. Mood stabilizing drugs are widely used for preventing recurrences of depression and for preventing and treating bipolar illness. They include lithium, which is sometimes used especially to prevent recurrence of depression, even if its use is limited in old patients for its side effects, the anticonvulsants carbamazepine and valproic acid. Putative last generation mood stabilizing drugs include the dihydropyridine L-type calcium channel blockers and the anticonvulsants phenytoin, lamotrigine, gabapentin and topiramate, which have unique mechanisms of action and also merit further systematic study. Psychotherapy is often used as an adjunct to pharmacotherapy, while electroconvulsant therapy is used only in the elderly patients with severe depression, high risk of suicide or drug resistant forms.

TCR and immunophenotype changes in dimethyl sulfoxide-dependent programmed cell death.

In the thymus most deleted cells are immature thymocytes and the high rate of cell death within the thymus is involved in the development of the initial T-cell receptor repertoire. Functional T-cell receptor recognition units are created by somatic rearrangements of gene segments, and the expression of successfully assembled TCR complex is the key to molecular events that culminate in T-cell activation, growth and differentiation. Previously, we reported that DMSO induces apoptosis in RPMI-8402 human pre-T cells. Here we examine the fate of pre-T cells undergoing negative selection analysing the responsiveness to DMSO-enforced TCR expression and immunophenotype modulation. Our results demonstrate that DMSO induces cell growth inhibition, cell phenotype changes, with down-regulation of CD2 and CD7, and increases in alpha/beta or gamma/delta TCR chains led by TdT, RAG-1 and RAG-2 activity. These modifications are associated with an apoptotic program. Taken together, these data suggest the existence of an early checkpoint that ensures in vivo the effective intrathymic differentiation supported from another point of view, the linkage between immunophenotypes and TCR regulation in T-cell differentiation and programmed cell death.

bcl-2, p53, and MIB-1 in human adult dental pulp.

Little is known about the renewal of some groups of cells in dental pulp, and the occurrence and significance of physiological cell death in dental pulp is not yet understood. The possibility of odontoblast disappearance by apoptosis has been proposed, and the presence of apoptotic cells in the rat and human odontoblastic and subodontoblastic layers has been recently described. bcl-2 and p53 are proteins involved in the apoptotic pathway, whereas MIB-1 is a proliferating cell marker. The aim of our study was an immunohistochemical evaluation of bcl-2, p53, and MIB-1 in healthy normal pulps of young human subjects. With bcl-2 immunostaining, some positive cells were found in the odontoblastic and subodontoblastic layers, whereas with MIB-1, only a few stromal cells were positive, and all odontoblasts were consistently negative. No cells were positive to p53. The bcl-2 immunoreactivity of the cells of the odontoblastic and subodontoblastic layers could help to explain the presence of apoptotic cells found in these regions.

Human recombinant interleukin-1 beta induces thromboxane A2 release in polymorphonuclear leukocytes, macrophages and platelets: effect of IL-1 receptor antagonist.

Prostaglandins and thromboxanes (Txs) are produced by polymorphonuclears (PMNs) and macrophages (Mphis) in response to various stimuli. PMNs were separated from other human blood cells and Mphis were separated from rat peritoneal lavage. In this paper we show that human recombinant interleukin-1 (hrIL-1) can stimulate the release of thromboxane B2 (TxB2) by PMNs and Mphis. In addition, we have shown that aggregation of PMNs may occur when calcium ions (7 mM) and hrIL-1 (100 ng/ml) are added to the cell preparation, but not when Ca2+ alone, hrIL-1 alone, or first hrIL-1 then calcium are added to the cell preparation. The treatment of human platelets with hrIL-1 shows that after 15 min incubation TxB2 is released. In addition, we compared the aggregation of platelets caused by ADP with that caused by hrIL-1. Human recombinant IL-1 at a concentration of 100 ng/ml also causes little aggregation of platelets, in this case the aggregation is reversible. In conclusion, hrIL-1 beta stimulates TxB2 release in PMNs, Mphis and platelets and this effect increases with addition of Ca2+ ions. The mixture of hrIL-1 and Ca2+ causes little aggregation of PMNs. In monocyte suspensions, pretreated with human recombinant IL-1 receptor antagonist (IL-1ra) 500 ng/ml for 10 min and then treated with LPS or hrIL-1 beta 10 micrograms/ml, the release of TxB2 was partially inhibited. IL-1ra may play a significant role in the control of IL-1 and LPS induction in the release of TxB2.

[Meningeal carcinosis: early clinical manifestations of inflammatory cancer of the breast]. / Carcinosi meningea: manifestazione clinica precoce di cancro infiammatorio della mammella.

Inflammatory carcinoma of the breast accounts for only 1-6% of mammary cancer in Caucasian women and is characterized by a poor prognosis; distant metastases frequently appear in fact in an early stage of disease and moreover metastatic spreading follows unpredictable ways. In this study we report on a case of a female patient in whom persistent signs of increased intracranial pressure, following the diagnosis of inflammatory carcinoma of the breast, have been referable to the tumour seeding the meninges in the absence of systemic disease. This peculiar and unusual form of neoplasia is up today a challenge for the clinician, both because of therapeutic difficulty and of unexpected metastases which, in turn, worsen the prognosis. Particularly, in our opinion, meningeal localization must be suspected even in the absence of distant metastases.

Immunocytochemical detection of factor XIII A--subunit in acute leukemia.

Factor XIII (FXIII) is a plasma pro-transglutaminase consisting of A and B subunits in a tetrameric structure. A cellular form of FXIII consisting exclusively of A subunits exists in platelets and monocytes: monocyte FXIII may be involved in connective tissue organization. To evaluate the expression and diagnostic significance of FXIII A subunit (FXIIIA) in acute leukemia, we performed an immunocytochemical study (PAP technique) with rabbit antiserum against FXIIIA on leukemic blasts of 48 cases. FXIIIA was detected only in myelomonocytic (M4), monocytic (M5) and megakaryocytic (M7) cases: in M4 and M5 samples the amount of blast cytoplasmic FXIIIA was closely correlated with the expression of monocyte-specific antigenic and cytochemical markers. Our data show immunocytochemical detection of FXIIIA to be useful for acute leukemia characterization.

The syndrome of abnormal chromatin clumping in leucocytes: clinical and biological study of a case.

The authors report the clinical and biological findings of a case of a rare haematological malignant entity, morphologically characterised by a bizarre nuclear abnormality in granulocytes, consisting of exaggerated chromatin clumping and apparent fragmentation of the nucleus, with a loss of segmentation. They emphasize the coexistence of proliferative and dysplastic characteristics as a distinctive marker of this disorder and suggest it may represent a distinct rare morphological entity among the atypical chronic myeloid leukaemias, Ph1 and ber negative.

Immunocytochemical detection of ferritin in human bone marrow and peripheral blood cells using monoclonal antibodies specific for the H and L subunit.

We have used the monoclonal antibodies 2A4 (specific for the H subunit of human ferritin) and LO3 (specific for the L subunit) for immunocytochemical detection of ferritin in bone marrow and peripheral blood cells from normal subjects and patients with various haematological disorders. Formalin-fixed slides were stained by the immunoalkaline phosphatase procedure (APAAP). In normal subjects, ferritin could be found only in bone marrow smears and appeared to be largely confined to erythroid precursors and reticuloendothelial cells. The more immature erythroid precursors contained higher concentrations of cellular ferritin. Although evaluation could be only semiquantitative, erythroblast ferritin appeared to be more reactive with the monoclonal 2A4 (15 +/- 7% positive erythroblasts) than with the monoclonal LO3 (6 +/- 5% positive erythroblasts), indicating that H-type ferritin was predominant, particularly in proerythroblasts and basophilic erythroblasts. By contrast, the ferritin present in reticuloendothelial cells appeared to be predominantly of L-type. Patients with iron deficiency showed low levels of positive erythroblast, whereas the reverse was true in patients with transfusional iron overload. Intense positivity for reticuloendothelial cell ferritin was found in patients with anaemia of chronic disease. In myelodysplastic syndromes and acute myeloid leukaemia (AML), ferritin positivity was generally very strong at any stage of erythroblast development, particularly with the monoclonal antibody 2A4. Perls-positive perinuclear granules of ring sideroblasts were not stained, confirming that mitochondrial iron deposition is not in the form of ferritin. In AML and myelodysplastic syndromes with excess of blasts, ferritin could be detected also in immature myeloid cells. These data indicate that: (a) in normal conditions ferritin is mainly expressed in red cell precursors and reticuloendothelial cells, and this is in keeping with the peculiar role of these cells in iron metabolism; (b) abnormal cell ferritin contents can be observed in both iron overload and malignancy.

Tumor necrosis factor alpha down-regulates c-myc mRNA expression and induces in vitro monocytic differentiation in fresh blast cells from patients with acute myeloblastic leukemia.

We have studied tumor necrosis factor alpha (TNF-alpha) for its capacity to induce differentiation and to modulate c-myc and c-fms protooncogene mRNA expression in fresh blasts from 10 patients with acute myeloblastic leukemia (AML). Bone marrow blast cells were grown in suspension cultures in the presence of 500 U/ml (62 ng/ml) of TNF-alpha for 7 days. Induction of differentiation was assessed by means of morphology, cytochemistry, immunophenotyping (CD11b, CD13, CD14, CD33), and nitroblue tetrazolium reduction. In all cases, exposure of leukemic blasts to TNF-alpha resulted in phenotypic changes consistent with induction of differentiation, although a marked variability in degree and type of response was observed. The majority of cases developed monocytic morphology and showed significant increases (chi 2 test, p less than 0.05) in phagocytic activity and/or expression of ANAE and myelomonocytic differentiation antigens (CD11b, CD14). TNF-alpha reduced c-myc mRNA level over a period of 24 hr in four of six cases studied: the two cases with no down-regulation were the least responsive in terms of myelomonocytic differentiation. These results confirm those obtained with leukemic cell lines, suggesting that TNF-alpha can induce differentiation of fresh AML blasts, mainly toward the monocytic lineage, and that induction of differentiation seems to be closely linked to down-regulation of c-myc mRNA expression over the first 24 hr rather than to attenuation of cellular proliferation per se.

5' Nucleotidase in chronic B cell leukemias: a cytochemical and ultrastructural study.

We studied by cytochemical means the distribution of 5' nucleotidase (5' NT), a purine degradative enzyme, in the circulating lymphocytes of 24 healthy donors and 41 cases of chronic lymphoid leukemias, classified according to morphological and immunological criteria. About half the normal circulating lymphocytes were 5'NT positive and exhibited variable degrees of enzyme activity. Among chronic B lymphocytic leukemias we found high percentages of positive cells only in the phenotypically more mature cases. Moreover all cases of hairy cell, follicular cell, lymphoplasmacytic, and plasma cell leukemia showed moderate or weak 5' NT reactivity. Also one case of chronic T lymphocytic leukemia, CD8 positive, was moderately positive, while another, with large granular lymphocyte morphology, was completely negative. Electron microscopy revealed a discontinuous, granular plasma membrane reaction pattern, varying in intensity from case to case. In conclusion, our results confirm the usefulness of the 5' NT cytochemical reaction for identification of lymphoid populations at different stages of maturation in chronic B cell disorders.

Biological and clinical features of acute lymphoblastic leukaemia with cytoplasmic granules or inclusions: description of eight cases.

We describe eight patients (four children and four adults) with an acute lymphoblastic leukaemia (ALL) with cytoplasmic granules or inclusions. The incidence of this variant of acute leukaemia in our whole series of patients with ALL is 1.8%. The granules or inclusions were usually positive for aspecific esterases (ANAE) and/or acid phosphatase, and the immunophenotype was in all cases typical of a CALLA positive B-lineage ALL (CD10+, CD19+ and/or CD24+, DR+, TdT+, anti-T-, anti-My-, SIg-). In one paediatric case, CD33 was unusually coexpressed. Ultrastructural investigations were performed in one case and demonstrated large granules containing vesicles, usually membrane bound, in the majority of blast cells. In the two cases analysed, Ig heavy chain gene rearrangement was detected. In this series of patients prognosis was poor since three never achieved a complete remission, four relapsed and only one is still in first continuous remission.

Reactive hemophagocytosis in Ki-l positive large cell lymphoma: a case study.

A case of large cell lymphoma presenting with hemophagocytic syndrome is reported. The clinicopathological findings suggested a diagnosis of malignant histiocytosis, but on the basis of immunohistological studies Ki-l lymphoma was diagnosed. Neoplastic cells expressed activation antigens such as HLA-DR, IL 2R, T10 and Ki-l, and showed high proliferative activity, but were devoid of T and B cell markers. The high percentage of reactive macrophages found in the bone marrow and lymph node probably reflected the release of lymphokines by the tumor population. The patient was treated with aggressive chemotherapy and is in complete remission at 8 months from diagnosis.

Cytochemistry of dipeptidylaminopeptidase IV in T lymphoblastic leukaemia-lymphoma.

The cytochemical distribution of dipeptidylaminopeptidase IV (DAP IV) was studied in 5 cases of T lymphoblastic leukaemic lymphoma and 12 cases of acute T lymphoblastic leukaemia, in order to ascertain differences between the enzyme positivity patterns of T cells at different stages of differentiation. Early thymic phenotype cases were almost completely negative; those of intermediate and mature thymic phenotype showed positivity in various percentages of blasts: either a single coarse granule or many coarse and small granules were detected. In mature phenotype cells a particularly intense DAP IV reaction was observed. In conclusion, our findings suggest that DAP IV reaction could be a useful tool for the cytochemical characterization of T acute leukaemia subtypes.

Tetrahydrofolate dehydrogenase cytochemistry in acute lymphoblastic leukemia.

We studied the cytochemical distribution of tetrahydrofolate dehydrogenase (FH4D), an enzyme involved in nucleic acid metabolism and thus in cell proliferation and differentiation processes, in bone marrow blasts from 37 cases of acute lymphoblastic leukemia (ALL), of whom 23 were pediatric patients. 26 cases were analyzed at onset, 11 in relapse. The ALL cases were immunologically classified as T (10), common (20), B (3) and null (4). In each subgroup the majority of lymphoblasts were positive, with heterogeneous positivity patterns and variable degrees of enzyme activity. Most T lymphoblasts were characterized by focal localization of FH4D, whereas in common blasts reactivity - usually less strong - was either focally localized or scattered with several fine granules. Finally, many B and null blasts showed diffuse positivity. A quantitative evaluation of FH4D activity using cytophotometric technique (Vickers M86) demonstrated higher degrees of reactivity in leukemic blasts than in normal lymphocytes. Moreover, slightly different levels of reactivity were observed in relation to immunological phenotype, age and stage of the disease. Therefore we think that FH4D is a useful additional marker for ALL characterization.