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Biomedical subjects

R Raimondi

Publications and source records attributed to R Raimondi.

At least 37 records · Page 2Linked to original sources
PubMed1995

Serologic and molecular evidence for a possible pathogenetic role of viral infection in CD3-negative natural killer-type lymphoproliferative disease of granular lymphocytes.

We studied a series of 18 patients with CD3- lymphoproliferative disease of granular lymphocytes (LDGL) for evidence of chronic viral infection, including Epstein-Barr (EBV), hepatitis B (HBV), hepatitis C (HCV), human T lymphotropic virus (HTLV), and human immunodeficiency virus (HIV). Although all patients tested had serologic evidence for past infection with EBV, polymerase chain reaction (PCR) analysis of peripheral blood mononuclear cell (PBMC) DNA utilizing specific EBV primers demonstrated the presence of EBV-DNA in only six of 17 CD3- LDGL cases. A previous history of HBV infection, as defined by the presence of circulating IgG anti-HBc antibodies associated with either HBsAg positivity or negativity, was documented in seven cases; however, viral DNA was not detected in PBMC of these patients using PCR with specific HBV primers. Specific anti-HCV antibodies, confirmed by recombinant immunoblot assay, were detected in five CD3- LDGL patients; PCR analysis demonstrated the presence of viral RNA in PBMC of two of these cases. No patient had antibodies to HTLV-I/II or HIV-1/2. Five patients were infected by more than one virus (two with HBV and EBV and three with HBV and HCV). Our results provide serologic evidence for past viral infection in the large majority of CD3- NK-type LDGL patients. These data suggest that viral infection may have played a role early in disease pathogenesis and may no longer be necessary in sustaining GL proliferation in CD3- NK-type LDGL.

Antigens, Viral↗
PubMed1993

Expression and functional role of tumor necrosis factor receptors on leukemic cells from patients with type B chronic lymphoproliferative disorders.

Two receptors for tumor necrosis factor (TNF) with different molecular weight (75-Kd and 55-Kd) and binding affinity have been recently discovered. To investigate the distribution and the functional role of these receptors on leukemic B cells from hairy cell leukemia (HCL) and B-cell chronic lymphocytic leukemia (B-CLL) patients, we evaluated: (1) the cytofluorimetric pattern of uncultured and cultured leukemic B cells incubated with utr-1 and htr-9 monoclonal antibodies (MoAbs), which specifically recognize the 75-Kd and 55-Kd TNF receptors (TNFR), respectively; (2) the effect of TNF-alpha and TNF-beta on leukemic B cells in an in vitro proliferation assay; (3) the role of anti-TNFR MoAbs on TNF-alpha and TNF-beta-driven B-cell growth; and (4) the proliferative effect of utr-1 and htr-9 MoAbs on in vitro cultured leukemic cells. Our study shows that the high affinity (75-Kd) but not the low affinity (55-Kd) TNFR molecules are expressed on freshly isolated leukemic B cells recovered from HCL and B-CLL patients. The expression of these receptors was neither upregulated nor downregulated by different stimuli, including TNF-alpha, TNF-beta, B-cell growth factor, and interleukin-2. TNF-alpha efficiently triggers the proliferation of HC and, to a lesser extent, the growth of B-CLL cells. TNF-beta was also able to transduce the proliferative signal in HCL, but not in B-CLL patients. TNF-alpha- and TNF-beta-driven B-cell proliferation was inhibited by the preincubation of leukemic B cells with utr-1 but not htr-9 MoAb. Moreover, anti-75-Kd, but not anti-55-Kd TNFR MoAb, was able to trigger the proliferation of leukemic B cells, and in particular of HC. These results show that leukemic B cells from patients with HCL and B-CLL are equipped with a fully functional high affinity TNFR.

Aged↗
PubMed1992

Role of tumor necrosis factor-alpha and its specific 55-Kd and 75-Kd receptors in patients with lymphoproliferative disease of granular lymphocytes.

The role of tumor necrosis factor-alpha (TNF-alpha) in the development of in vitro proliferative and cytotoxic abilities of granular lymphocytes (GL) in patients with lymphoproliferative disease of GL (LDGL) has been investigated. To this aim, taking advantage of the recent generation of specific monoclonal antibodies (MoAbs) reacting with the p55 and p75 TNF receptors (TNF-R) (htr-9 and utr-1 MoAb, respectively), we evaluated the expression and the functional role of each TNF-R in freshly isolated highly purified GL from a series of 10 LDGL patients (six CD3+ T-lineage GL and four CD3- natural killer [NK]-lineage GL). The expression of TNF-alpha transcripts and the release of TNF-alpha in the culture medium at resting conditions and following cell activation were also studied. Our data indicate that at resting conditions both CD3+ and CD3- GL express only the p75 TNF-R. Accordingly, a specific inhibition of phycoerythrin (PE)-conjugated TNF-alpha binding was demonstrated by the anti-p75 TNF-R utr-1 MoAb, but not by the anti-p55 htr-9 MoAb. Following activation with interleukin-2 (IL-2), anti-CD3, or anti-CD16 MoAbs, an increased expression of the p75 TNF-R and a slight induction of the p55 TNF-R was observed. Weak expression of specific TNF-alpha transcripts was detected at resting conditions and on unstimulated cells, whereas both IL-2 or anti-CD3 MoAb induced TNF-alpha mRNA. Under these in vitro conditions, detectable amounts of this cytokine were demonstrated in the culture supernatant of GL. The cytotoxic and proliferating activities mediated by IL-2 or anti-CD3 MoAb were dampened by anti-TNF-alpha antibody, suggesting a role for endogenous TNF-alpha in these functions. Both utr-1 and htr-9 MoAbs showed a moderate inhibition of proliferative activity, whereas cytotoxicity was not reduced. Taken together, our results suggest that TNF-alpha plays a role in the mechanisms leading to CD3+ and CD3- GL in vitro activation in patients with LDGL.

Aged↗
PubMed1991

[Relationship between nutritional and immunologic status in patients with esophageal cancer].

The nutritional and immunological status have been evaluated in 28 consecutive patients with esophageal cancer. Patients (21 male and 7 female), had a mean age of 61 years, ranging from 34 to 84 years. The tumor histological type was squamous in 25 patients. A melanoma, an oat cell carcinoma and a adenocarcinoma were observed in the remaining cases. The nutritional status was assessed by means of weight loss, triceps skinfold, midarm muscle circumference and serum levels of albumin and transferrin. On the basis of this data the patients were divided into two groups: A, 19 patients (68%), normal nourished group (or with a mild malnutrition) and B, 9 patients (32%) with a severe malnutrition. The immunological status was assessed by determining the lymphocyte absolute number (H-6000-Technicon), the T-Lymphocyte sub-populations (flow-cytometry with monoclonal antibodies--Ortho Diagnostic System) and the patient's response to intradermally placed recall antigens (Multitest Merieux). Significative immunological abnormalities were found only in malnourished patients, group B (p less than 0.05). Moreover a reduction of OKT4 helper (less than 30%) and the inversion of OKT4/OKT8 ratio (less than 0.9%) were also observed only in the malnourished group (p less than 0.01). Therefore, we conclude that acquired immunodeficiency, when present in patients with esophageal cancer, is due to the severe malnutrition rather than to the cancer itself.

Adult↗
PubMed1990

Cell membrane expression and functional role of the p75 subunit of interleukin-2 receptor in lymphoproliferative disease of granular lymphocytes.

The cell membrane expression and functional role of the interleukin-2 receptor (IL-2R) was analyzed in nine patients with lymphoproliferative disease of granular lymphocytes (LDGL) using monoclonal antibodies (MoAbs) specific for the p75 (TU27) and the p55 (anti-Tac) subunits of IL-2R. Four patients were characterized by the proliferation of CD3+CD8+ granular lymphocytes (GL) expressing the alpha/beta T-cell receptor (T alpha beta) and one case by the proliferation of CD3+CD4-CD8- GL expressing the gamma/delta T-cell receptor (T gamma delta); in four additional cases proliferating cells were CD3 negative GL. Consistent with data observed on normal GL, phenotypic analysis demonstrated that patients' GL lack the expression of the p55 IL-2R, whereas the p75 subunit is constitutionally expressed by expanding GL of both T-cell (either T alpha beta and T gamma delta) and natural killer (NK) origin in variable proportions (11% to 94% of cells). The analysis of the cytotoxic and proliferative activity demonstrated that the anti-p55 MoAb failed to inhibit IL-2-mediated activation, whereas a marked inhibition of both cytotoxicity and proliferation were obtained using the anti-p75 chain specific MoAb. These data indicate that the p75 chain of IL-2R is responsible for IL-2 signal transduction in both CD3+ and CD3- LDGL patients' GL.

Adult↗
PubMed1990

Mechanisms accounting for the defective natural killer activity in patients with hairy cell leukemia.

Natural killer (NK) cell activity is severely impaired in untreated patients with hairy cell leukemia (HCL). In an attempt to investigate whether this impairment is related to a defect at the target cell binding and/or at the post target cell binding level, we evaluated the peripheral blood mononuclear cells (PBMC) of HCL patients for their ability to: (1) bind and kill K-562 NK-sensitive targets at the single cell binding level; (2) release the NK cytotoxic factor (NKCF) under different in vitro stimuli, including K-562 and phytohemoagglutinin; and (3) kill K-562 targets in a lectin-dependent cellular cytoxicity (LDCC) assay. This study demonstrates that untreated HCL patients' PBMC show a low ability to form conjugates with K-562 targets at the single cell binding level (5.7% +/- 1.0%) with respect to patients studied after treatment (9.3% +/- 1.3%) and controls (15.0% +/- 4.0%); P less than .05 and P less than .001, respectively. A decreased ability to kill the bound target was demonstrated in untreated cases (1.2% +/- 1.1%) versus patients studied after treatment and controls (12.3% +/- 1.6%, 17.0% +/- 3.1% respectively); P less than .001 in both conditions. After activation of effector cells with interleukin-2 (IL-2) in vitro, an increase in the ability of PBMC to form conjugates with K-562 targets and kill the bound target was demonstrated in each group of patients. Moreover, IL-2 was able to increase the cytotoxicity against NK-sensitive targets in all patients tested. Evaluation of NKCF production showed that untreated patients release low levels of NKCF when PBMC were incubated in the presence of K-562 stimulators (1.8% +/- 0.7%) with respect to patients after interferon-alpha (IFN-alpha) therapy (7.6% +/- 2.1%) and controls (12.9% +/- 2.2%); P less than .02 and P less than .001, respectively. When the recognition mechanisms were bypassed by triggering the cells with lectins in an LDCC assay, we demonstrated an increase of the lytic activity in both groups of patients with respect to the baseline values. However, the cytotoxic capacity observed in untreated patients was significantly lower than that observed in subjects after IFN-alpha therapy and controls (P less than .001). These findings suggest that the impaired NK activity observed in patients with HCL is related to defects both at the target and posttarget cell binding levels.

Adult↗
PubMed1984

Non-T, non-B childhood acute lymphoblastic leukemia. Correlation between cytochemical markers and first complete remission.

The positivity for four cytochemical reactions, acid phosphatase (AcP), alpha-naphtyl acid acetate esterase (ANAE), beta-glucuronidase (BG), and N-acetyl beta-glucosaminidase (NABG) was correlated to first remission duration in 120 children affected with non-T, non-B acute lymphoblastic leukemia (ALL). The percentages of patients remaining in complete remission at 72 months were always higher for children whose blasts lacked these enzymatic reactions; however, a statistical difference was found only between BG+ and BG- ALL. It also appears that more complete enzymatic patterns of leukemic cells are associated with a poorer prognosis. The percentage of patients still in their first remission was 89% for leukemias with no cytochemical markers, 59% when one reaction was present, but less than 39% when two or more enzymes were detected in the blasts. It is noteworthy that the blasts of patients with more severe prognosis demonstrated a simultaneous positivity for AcP-ANAE or BG-NABG cytochemical reactions. The possible usefulness of these cytochemical markers to detect subsets of patients with different prognostic significance among non-T, non-B ALL is discussed.

Acid Phosphatase↗
PubMed1984

Characterization of two patients with lymphomas of large granular lymphocytes.

Two patients with non cutaneous well-differentiated lymphocytic lymphoma with leukemic spread are reported. The large majority of their peripheral blood mononuclear cells (PBMC) formed rosettes with sheep erythrocytes, had receptors for the Fc portion of IgG, and an enzymatic profile of relatively mature T-cells. These cells were morphologically characterized as large granular lymphocytes. Studies with monoclonal antibodies in one of the cases showed an OKT3+, OKT10-, OKT4-, OKT8-, HNK-1-, OKM1+ phenotype, whereas PBMC from the other case were OKT3+, OKT10-, OKT4-, OKT8+, HNK-1+, OKM1-. PBMC from the first patient were able to suppress in vitro B-cell differentiation and were capable of a strong antibody dependent cellular cytotoxicity (ADCC) activity. Natural killer (NK) activity was reduced. Cells from the other patient who was hypogammaglobulinemic, exerted suppressor activity in immunoregulatory assays, and showed ADCC and NK activity. These data support the existence of LGL lymphomas consisting of the proliferation of mature appearing cells capable of functional activity.

Antibodies, Monoclonal↗
PubMed1984

T antigen expression by human lymphocytes in relation to E rosette affinity.

Active and late rosette-forming cells, separated on the basis of their different affinities for SRBC, were tested for their ability to react with monoclonal antibodies of the OKT series. No significant preferential distribution of T subpopulations defined by these reagents was found in the high affinity E rosette fraction, while in the low affinity T cell subset the major finding was a high number of cells lacking both OKT4 and OKT8 determinants. This seems to be related to methodology, as indicated by experiments in which sequential cycles of rosetting procedures were found to induce loss of reactivity with OKT monoclonal antibodies. The implications of these methodological observations are further discussed.

Adult↗