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Di Gennaro A, Marini L, D’Ostilio A, Loreto MF, Modesti M, Scipione MS, Ginaldi L, De Martinis M, Quaglino D
No full textChanges in B cell antigen expressions in the elderly
No full textPO-0999 Changes in B cell antigen expression in the elderly
Ginaldi L, De Martinis M, D’Ostilio A, Marini L, Loreto MF, Profeta VF,*
Quaglino D
Department of Internal Medicine and Public Health, University of
L’Aquila, *Ser. T ASL Teramo, Italy
The involvement of the B cell compartment during senescence plays an
important role in the development of the immune dysfunction (e.g. hypergammaglobulinemia,
autoantibody production and impaired responses to
immunisations). In order to identify specific antigen expression changes on
B lymphocytes which may contribute to the immune deficiency in the elderly,
we investigated, by triple staining flow cytometry, the level of expression
of some constitutive surface markers (HLA-DR, CD19, CD20) and of a
series of adhesion molecules (CD49b, CD49d, CD50, CD62L) on B lymphocytes
from 23 healthy elderly individuals (82-100 years old, mean age
92) compared to 13 healthy young donors (20-50 years old, mean age
31). All aged donors fullfilled the admission criteria for gerontological studies
proposed by the Senicor Protocol. Both percentage and absolute number
of B lymphocytes (CD19+ and CD20+ cells) were significantly
decreased in the elderly compared to young donors. The absolute number
of B cells expressing the adhesion molecules CD49b and CD49d was lower
in elderly individuals, as well as the percentage value of B cells expressing
the adhesion molecules CD50 and CD62L. The percentage and
absolute number of B cells coexpressing the CD5 antigen was decreased
in elderly subjects. The CD20 expression antigen was increased on B lymphocytes
coexpressing the CD49b and CD49d in elderly donors compared
to young subjects. Also the CD5 density on B cells from old donors was
slightly increased compared to controls. No differences were detected in
the expression of CD19, CD50, CD49b, CD49d, CD62L and HLA-DR molecules
on B lymphocytes. Quantitative flow cytometry may be of value in
the elderly both for clinical and biological studies. The study of antigen density
changes on B cells in the elderly may allow a better understanding of
the humoral immune defects observed in these subjects and provide
insights into the functional defects of the B cell compartment characterising
immunosenescence
Blood coagulation changes and neoplastic pathology
No full textCancer patients show an increased susceptibility to develop thromboembolic diseases, suggesting that disorders of coagulation are very common in this pathology. Tumor cells possess the capacity to interact with the hemostatic system, activating the coagulation cascade and stimulating the prothrombotic properties of other blood cell components; the same events while inducing a hypercoagulable state, also contribute to the processes of tumor growth, neoangiogenesis and metastatic formation. Multiple risk factors associated with malignant disease contribute to the hypercoagulability state: stasis induced by prolonged bed rest, vascular invasion by the tumor and iatrogenic complications including the use of central vein catheters and chemotherapy. Several tests have been developed to assess the hypercoagulable state, however their clinical significance still needs to be defined, especially in terms of their predictive value for thrombosis. Clinical manifestations vary from localized deep venous thrombosis (DVT) or pulmonary embolism, more generally associated with solid tumors, to disseminated intravascular coagulation, frequent in hematologic malignancies and metastatic cancer. Diagnosis of idiopathic DVT, in the absence of other risk factors, could indicate the presence of occult cancer, but the usefulness of an extensive work-up to detect malignancy in terms of cost to benefit ratio still has to be demonstrated. Patients with cancer and thromboembolism must be treated with anticoagulant therapy; a large number of studies have shown that either low molecular weight heparins or standard unfractionated heparin for the treatment of acute deep vein thrombosis in hospitalized patients are equally safe and effective; however, the first treatment has been reported to be associated with a lower mortality. After an episode of thrombosis the patients should be protected by a long term course of oral anticoagulation, remaining high the risk of recurrence for as long as the cancer is active
Flow cytometry in the study of acute leukaemias: II. Its role and relationship to other cytobiological techniques
No full textFlow cytometry has became an extremely
useful tool in thè diagnosis of hematological malignancies.
The multitude of available monoclonal antibodies
and thè routine use of multiparametric
techniques bave drastically improved thè diagnostic
utility of flow cytometry in thè study of leukemias.
This review focuses on thè use of flow cytometry in
thè routine clinicopathological approach to thè diagnosis
of acute leukemias. The Authors discuss not
only thè use of flow cytometry in thè differential diagnosis,
but also correlate flow cytometric immunophenotyping
with other cytobiologic techniques
in thè study of acute leukemia
Immunological changes in the elderly
No full textImmunosenescence is a complex remodelling of the immune system which may contribute significantly to morbidity and mortality in the elderly. Much evidence suggests an association between immune function and longevity. It was advanced that individuals who have survived in good health to the maximum life span are equipped with optimal cell defense mechanisms. Despite the great number of studies on the immune system in the elderly, little is known of the biological basis of immunosenescence in humans. This is partly due to the contrasting results often obtained by the various investigators. One source of discrepancy is that diseases are frequent in aging, and the alterations observed in the immune parameters of the elderly could be a cause or alternatively a consequence of the underlying pathological processes. Undoubtedly some diseases to which aged people are particularly susceptible, such as infectious, autoimmune and neoplastic pathologies, include dysregulation of several immune functions in their pathogenesis. On the other hand, recent studies in healthy centenarians suggest that the immunological changes observed during aging are consistent with a reshaping, rather than a generalized deterioration, of the main immune functions. Considering that the number of old people is dramatically increasing, and that geriatric pathology is becoming an important aspect of clinical practice, it seems particularly interesting to review the peculiar findings in the immune system of the elderly so as to better understand their susceptibility to certain diseases, and the links between health and longevity
Adhesion molecules on peripheral blood lymphocyte subpopulations in the elderly
No full textAdhesion molecules, such as CD49d, CD50 and CD62L, have important roles in many adhesive interactions involving cells of the immune system. Since it has been shown that many immunological alterations are present in aged subjects, we studied, by means of triple colour whole blood immunostaining and multiparametric flow cytometry, the expression and intensity level (MFI) of these molecules on peripheral blood lymphocyte subpopulations from 23 healthy elderly subjects and 13 young controls. In the elderly a decrease in total peripheral blood lymphocytes bearing CD62L antigen was observed (39 +/- 13% vs 63 +/- 6% and 745 +/- 312/mm3 vs 1,393 +/- 407/mm3; p<0.001), whereas the numbers of lymphocytes expressing CD49d and CD50 antigens were comparable in aged and young subjects. In addition, CD50 and CD62L MFI values on total peripheral blood lymphocytes were higher in elderly than in young subjects (5.23 +/- 1.03 vs 4.18 +/- 0.44, p = 0.001 and 2.60 +/- 0.35 vs 2.21 +/- 0.40, p = 0.005 respectively) while the intensity expression of CD49d was unchanged. The percentages and absolute numbers of T and B lymphocytes expressing CD62L were decreased in elderly compared to young subjects (CD62L+CD3+: 43 +/- 15% vs 66 +/- 9% and 581 +/- 257/mm3 vs 1,028 +/- 418/mm3, p<0.001; CD62L+CD19+: 78 +/- 12% vs 90 +/- 4%, p < 0.005 and 103 +/- 64/mm3 vs 207 +/- 98, p < 0.001). A decrease in the proportion of CD62L bearing NK cells was also observed in the elderly (25 +/- 14% vs 46 +/- 24%, p<0.005), although their absolute number was unchanged. No significant differences were detected in the proportion of T, B and NK lymphocytes expressing CD49d and CD50 antigens and only the absolute numbers of B cells expressing these adhesion molecules were lower in elderly (CD49d+CD19+: 121 +/- 71/mm3 and CD50+CD19+: 107 +/- 73/mm3) compared to young donors (CD49d+CD19+: 248 +/- 112/mm3 and CD50+CD19+: 235 +/- 120/mm3, p < 0.001). Moreover, the intensity of adhesion molecule expression was differentially modulated in the elderly depending on the specific lymphocyte cell population considered. The densities of CD49d, CD50 and CD62L antigens on B and NK lymphocytes from the two age groups were not different; on the contrary, T lymphocytes from elderly donors exhibited increased CD49d (1.69 +/- 0.09 vs 1.62 +/- 0.07, p < 0.05), CD50 (4.98 +/- 1.16 vs 3.77 +/- 0.46, p < 0.001) and CD62L (2.26 +/- 0.38 vs 1.99 +/- 0.37, p < 0.05) MFI values compared to young donors
Immunosenescence and Infectious diseases
No full textInfectious diseases are major causes, with malignancies, of morbidity and mortality in the elderly. Increased susceptibility to infections may result from underlying dysfunction of an aged immune system; moreover, inappropriate immunologic functions associated with aging can determine an insufficient response to vaccines. Impairments of cellular, humoral and innate immunity in the elderly, contributing to increased incidence of infectious diseases, are discussed in this review
Peristalsis regulation by tachykinin NK1 receptors in the rabbit isolated distal colon
Full text linkFlow cytometry in the study of acute leukaemias: I. Technical considerations
No full textFlow cytometry has became an important
method for thè study of acute as well as chronic
leukemias. In particular, it is a useful method for
thè lineage assignment and maturational analysis of
malignant cells. A knowledge of thè basics of flow cytometry,
technical aspects of instrumentation and
new developed techniques such as multiparametric
analyses and quantitation of density antigens are reviewed.
The Authors discuss thè most common applications
of flow cytometry in thè study of acute
leukemia
Coagulation and cancer: implications for diagnosis and management
No full textCoagulation disorders are a common problem in neoplastic patients and many factors contribute to increase the risk of thromboembolic events in these patients. An hypercoagulable state is induced by malignant cells interacting directly with hemostatic system and activating the coagulation cascade. More sensitive tests to assess an hypercoagulable state in cancer patients have been developed; even though these tests are always altered in cancer patients, none of them possess a clinical significance in terms of predictive value for the occurence of thromboembolism and disease prognosis in the individual patient. The most frequent thromboembolic complications in cancer patients are deep vein thrombosis of the lower extremities and pulmonary embolism; therefore, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura or haemolytic uremic syndrome are special manifestations of neoplastic disease. Diagnosis of idiopathic deep vein thrombosis, in the absence of other risk factors, could indicate the presence of occult malignant disease; however, the need for an extensive work-up to detect malignancy is still controversial. Neoplastic patients showing a thromboembolic event should be treated with unfractioned heparin or, alternatively, with low molecular weight heparins. In order to prevent recurrence, the administration of heparin should be associated and followed by an oral anticoagulant drug. In recent years new approaches in anti-aggregation therapy have been studied, such as COX-inhibitors, cicaprost and ReoPro; further studies are needed to determine the usefulness of these molecules in treatment of malignancies
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