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Biomedical subjects

L Tesio

Publications and source records attributed to L Tesio.

53 records · Page 3Linked to original sources

Phenotypic, cytogenetic and molecular characterization of a new B-chronic lymphocytic leukaemia (B-CLL) cell line.

A lymphoid cell line was established from a patient with B-cell chronic lymphocytic leukaemia (B-CLL) by infecting blood lymphocytes with Epstein-Barr virus (EBV). Immunoglobulin gene rearrangement studies and the presence of a chromosome marker (isochromosome 17q) provided the formal proof that the line has originated from the neoplastic B cells. The morphology and phenotype indicate that the EBV-induced cell line has reached a plasma cell-like stage of differentiation.

B-Lymphocytes↗

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↗

Cytoskeleton organization is aberrantly rearranged in the cells of B chronic lymphocytic leukemia and hairy cell leukemia.

The organization of actin-containing microfilaments and vimentin-containing intermediate filaments has been investigated in B chronic lymphocytic leukemia (B-CLL), hairy cell leukemia (HCL), and normal B cells cultured in vitro under basal conditions and after induction with 12-O-tetradecanoyl-phorbol-13-acetate (TPA). In uninduced B-CLL cells, F-actin was predominantly associated with dot-shaped structures scattered over the ventral membrane representing spotty close contact adhesion sites analogous to "podosomes" described in other cell types. On TPA induction, podosomes became clustered in sharply defined areas sitting in the cell center beneath the nucleus. In some cells, long actin-containing protrusions appeared. In HCL cells, F-actin was associated with thin microvilli responsible for the "hairy" appearance; occasional cells showed scattered podosomes. On TPA induction, HCL cells sprouted long dendritic processes rich in submembraneous F-actin, which made intertwined networks. Therefore, in both B-CLL and HCL cells, adhesion structures were present and the capacity for adhesion in vitro was marked, which might explain some peculiar clinical features of the diseases. Adhesion structures and adhesive properties never appeared in normal B cells. These data further support the notion that B-CLL and HCL, although clinically different, may share common biological features and suggest that in these disorders, cytoskeleton modifications may represent a hallmark of transformation.

Actin Cytoskeleton↗

Speed-dependent variations of lower-limb joint angles during walking. A graphic computerized method showing individual patterns.

A method for obtaining a synthetic representation of the joint angle time-courses at different walking velocities is presented, based on a computerized procedure. Hip, knee and ankle joint angles are measured by electrogoniometric devices and checked on line for their reliability. One stride only for each walking speed is selected as representative of the adopted cadence. For each joint a tridimensional representation of angle time-course versus stride frequency or versus gait speed is performed so that speed-dependent variations can be analyzed. Ten normal (seven males and three females) and three prosthetized subjects have been tested by this method. In normal as well as in pathological subjects individual features could be easily detected and the method proved to be useful for a functional gait evaluation.

Adult↗

A possible pathogenetic role of cationic proteins (CP) released by stored granulocytes in the development of pulmonary infiltrates after granulocyte transfusions.

The cationic protein (CP) content of polymorphonuclear neutrophils (PMN) prepared for transfusion is depleted after storage. The supernatants from these PMN have in vitro a PMN aggregating activity which is abolished by the preabsorption with a specific rabbit anti-human PMN CP serum. Furthermore, when the supernatants stored for few hours were injected into New Zealand White rabbits, a marked sequestration of PMN took place in the lung microvascular bed. It is suggested that PMN storage per se can cause the release of intracellular mediators of possible pathogenetic importance in the development of the pulmonary infiltrates observed after PMN transfusions.

Adult↗

Identification of malignant plasma cell precursors in the bone marrow of multiple myeloma.

Precursors of plasma cells were studied in the bone marrow of 28 patients with multiple myeloma, plasma cell leukemia, and benign monoclonal gammopathy. Pre-B and B cell populations were analyzed with anti-B monoclonal antibodies corresponding to the clusters standardized at the Leucocyte Typing Workshops in Paris and Boston (CD9, CD10, CD19-22, CD24). In advanced forms of plasma cell malignancies, such as cases of multiple myeloma in stages II and III and of plasma cell leukemia, some cells of lymphoid morphology expressed common acute lymphoblastic leukemia antigen (CALLA, CD10) and HLA-DR, but contained no detectable terminal deoxynucleotidyl transferase enzyme. These CALLA+ cells were absent in benign monoclonal gammopathies. In multiple myeloma, the CALLA+ cells were negative for surface and cytoplasmic immunoglobulins (Ig), and, unlike CALLA+, terminal deoxynucleotidyl transferase (TdT+) pre-B cells in the normal bone marrow also failed to react with antibodies to B cell-associated antigens such as CD9, CD19, CD22, and CD24. The CALLA+, Ig- cells could be regarded as preplasmacytic since, after having been separated and stimulated with the phorbol ester 12-0-tetradecanoyl-phorbol-13 acetate in vitro, they transformed into plasma cells and synthesized the same heavy and light chains as myeloma cells.

Adult↗

HLA-Dr+ T cells of the Leu 3 (helper) type infiltrate the kidneys of patients with systemic lupus erythematosus.

The lineage and distribution of mononuclear cells infiltrating the kidneys of patients with systemic lupus erythematosus (SLE) have been investigated in cryostat tissue sections of biopsies from 11 patients. The use of heterologous antisera and monoclonal antibodies has revealed that: B lymphocytes and plasma cells are virtually absent in SLE kidney specimens; The vast majority of mononuclear cells which infiltrate the interstitium are activated (HLA-Dr+) T cells (Leu 4+) presenting the helper (Leu 3+) phenotype; T cells are absent in the glomeruli, where HLA-Dr+, SIgM-, Leu 4- elements with a macrophage like appearance can be observed.

Adult↗

Phorbol ester induces abnormal chronic lymphocytic leukemia cells to express features of hairy cell leukemia.

We have investigated the relationship between chronic lymphocytic leukemia (CLL), hairy cell leukemia (HCL), and different normal B cell subsets: Mrbc+, T1+ and slgM+ tonsil cells; germinal center; mantle zone; and peripheral blood B lymphocytes. Both malignant and normal cells were incubated in vitro with the phorbol ester 12-O-tetradecanoyl-phorbol-13-acetate (TPA) for 72 hours and the morphology, cytochemical profile, and surface markers were evaluated. The results show that CLL cells TPA-induced become indistinguishable from HCL by four independent criteria: the morphology; the cytoplasmic tartrate resistant acid phosphatase (TRAP) enzyme activity; the membrane positivity with anti-Leu M5 (SHCL3); and anti-Tac monoclonal antibodies which, in the uninduced state, react only with HCL. The features of TRAP and Tac positivity are also expressed (though in variable degree) by different normal B cell populations activated with TPA or pokeweed mitogen (PWM). It is concluded that HCL might represent an aberrantly activated variant of CLL (or of a CLL-related disorder).

Acid Phosphatase↗

Motion of the center of gravity of the body in clinical evaluation of gait.

The motion of the center of gravity during walking was analyzed in five hemiplegic subjects and eleven subjects affected by unilateral hip arthritis. In the hemiplegic subjects and 6 subjects with hip arthritis the transfer between kinetic and potential energy (with a passive pendular motion) was found to be 9-95% greater during the step performed on the affected limb ("pathological" step); as a consequence, the muscular work done during this step was 7-81% of the work done during the step performed on the second limb ("normal" step). Qualitatively similar gait anomalies were recorded in all hemiplegic subjects with hypertonus of the paretic limb: these subjects had to lift the spastic limb as a whole during the normal step, with the consequence that the center of gravity was lifted 0.6-3 cm more than during the pathological step. In contrast, various motor patterns were found in patients with hip arthritis. During the pathological step the center of gravity reached a height 0.5-3 cm greater in 7 subjects, 1 cm smaller in one subject, and about the same height reached during the normal step in 3 subjects. This was consistent with the various motor deficits caused by hip arthritis.

Aged↗

Ergometric evaluation of pathological gait.

At each step of walking, the center of gravity of the body moves up and down and accelerates and decelerates forward with a combined movement that allows an appreciable transfer (R) between gravitational potential energy and kinetic energy, as occurs in a pendulum. The positive work and power to lift the center of gravity, to accelerate it forward, and to maintain its motion in a sagittal plane, the amount of R, the maximal height reached during each step by the center of gravity, and the step length and frequency are all determined by a microcomputer a few minutes after a subject walks on a force platform. This method is applied to the analysis of pathological gait in the attempt to measure quantitatively the alteration of the normal locomotory movement of the center of gravity. The strides of the patient are compared with the strides of normal subjects; in addition, the movement of the center of gravity of the patient during the stance on the affected limb is compared with the movement of the center of gravity during the stance on the unaffected limb, thus giving an index of the asymmetry of locomotion.

Adult↗

Short form of the Dizziness Handicap Inventory: construction and validation through Rasch analysis.

A new item response scale is presented, which measures the severity of self-reported balance deficits. The scale, DHIsf, is a short form of the Dizziness Handicap Inventory. The scale was constructed and validated by Rasch analysis. Rasch analysis was applied to rescore or remove any items misfitting, redundant, or off-target, until an optimal instrument was obtained. The 25-item, 3-level Dizziness Handicap Inventory was, thus, reduced to the 13-item, 2-level DHIsf. The retained items explore the domains of eye/head movements, full body activities, and mood alterations. Data were collected from 55 outpatients (63 +/- 13 yr; 43 females) attending otoneurological rehabilitation referral at a general hospital because of complaints of dizziness or imbalance. They were fully independent in ambulation and showed no evidence of major neurological or orthopedic diseases. Objective tests included brain computed tomography, sovraaorctic Doppler sonography, craniocorpography, static posturography, and nystagmography. The findings were categorized as pathologic, borderline, or normal. At least one examination was borderline or abnormal in 42 patients. The DHIsf was well targeted on this sample, with a mean score of 5.7/13 (standard deviation, 2.8; median, 5; range, 1-13). The Rasch statistics showed that the 13 items evenly fitted a hierarchy of difficulty within a homogeneous construct. A moderate but significant variance explanation of DHIsf measures was provided by a two-way analysis of variance model, with craniocorpography and nystagmography as independent categorical variables (r2 = 0.15; P = 0.018). When the clinical tests were individually taken into account, their outcome (dichotomized as abnormal v borderline or normal) could not be predicted by either of the DHIsf measures or raw scores (logistic regression). The DHIsf compares favorably with the original Dizziness Handicap Inventory, shows some consistency with the instrumental findings, and provides original information on the severity of imbalance syndromes, as it is seen from the patient's perspective.

Activities of Daily Living↗

Life Satisfaction Index: Italian version and validation of a short form.

The Life Satisfaction Index-version A (LSIA) is a 20-item questionnaire providing a cumulative score acknowledged as a valid index of quality of life. In the present study, an Italian version was produced through validated procedures of repeated back-translations. The final Italian version (LSIA.it) was administered to 90 healthy subjects (55 women; aged 40-65 yr, median 51). Cronbach alpha was 0.74, in agreement with previous studies on English, Greek, and Spanish versions, suggesting satisfactory internal consistency of the scale. Also in agreement with previous studies, factor analysis identified three factors (mood tone, zest for life, and congruence between desired and achieved goals), with eigenvalues of 2.80, 1.72, and 1.34, respectively. Nine of the original 20 items were dropped because of inconsistency with the overall scale and/or because of ambiguous loading onto the extracted factors. The resulting 11-item short form (LSI-11) had alpha = 0.69 and Kaiser-Meyer-Olkin measure of sample adequacy = 0.65. In our sample, the mean score of LSIA.it was almost the same as that previously reported in the literature for LSIA, and the correlation between LSIA and LSI-11 was very high (r = 0.91). In a test-retest trial, the cumulative score of LSI-11 showed a percentage of agreement ranging from 73.9 to 100 and Cohen's k statistic for reliability ranging from 0.51 to 1. The individual items of the LSI-11 presented substantial (k > 0.6) to excellent (k > 0.8) levels of agreement. The responsiveness of LSIA and LSI-11 during a hospital stay for 30 consecutive inpatients for medical rehabilitation programs, as measured by effect size, was 0.57 and 0.63, respectively. The results suggest that (1) the LSIA it has cultural equivalence with the English LSIA and that (2) the 11-item short form of LSIA is not only simpler but also more valid from a psychometric standpoint.

Achievement↗

A short measure of balance in multiple sclerosis: validation through Rasch analysis.

Ambulatory patients with multiple sclerosis (MS) frequently present with poor balance. Neither static nor dynamic posturography explore balance during self-paced movements in real-life activities, when fall is most probable. Behavioural item-response scales can easily represent these activities. However, testing many items can easily cause fatigue in MS patients, thus distorting their scores. On the other hand, the lower the number of items, the lower the precision of the cumulative score and its reliability. A new short instrument was derived from existing ones (the Tinetti and the Berg balance scales). A preliminary 10-item version encompassed sit/stand manoeuvres, standing with eyes open and closed, standing with eyes closed and head extended, leaning forward while standing, picking up an object from floor, resisting nudges on the sternum, turning around, tandem stance. The instrument was administered 1-3 times to 55 MS patients (103 observations overall), all of them able to walk autonomously for at least 20 metres. The Rasch Analysis was adopted to explore the psychometric validity of the scale. Two items (Stand-to-sit and Standing with eyes open) were deleted, as they were too easy and thus uninformative. The remaining 8 items made up a scale (called EQUI-SCALE) complying with the requirements of unidimensionality and reliability. The item scores remained stable in a sub-sample of 24 patients tested before and after ten 1-hour exercise sessions, thus supporting the homogeneity of the items.

Adult↗