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Biomedical subjects

F Grignani

Publications and source records attributed to F Grignani.

At least 145 records · Page 8Linked to original sources

Phenotypic dissection of cord blood immunoregulatory T-cell subsets by using a two-color immunofluorescence study.

Expression of TQ1(Leu8) and 2H4 antigens on human cord blood T-cell subsets was evaluated by a double immunofluorescence analysis. In normal adult blood all of the helper function for B-cell differentiation is confined to the smaller OKT4+TQ1-(Leu8-) cell subset, while the OKT4+TQ1+(Leu8+) cell subpopulation includes a subset of suppressor inducer 2H4+(JRA+) cells. Our results indicated that the OKT4+TQ1-(Leu8-) cell subpopulation was decreased and the reciprocal OKT4+TQ1+(Leu8+) cell subset was markedly increased in cord blood E-rosetting OKT3+ cell population. A rise in the number of cord OKT4+2H4+ cells was also found. In addition, TQ1 antigen was present on OKT3+E-, a less mature, cord T-cell subset, not present in adult blood. These findings may not only be of help in understanding lymphoid cell development during ontogeny, but also may agree with the reported strong-suppressor and weak-helper activities exerted by the T-cell subsets circulating in human cord blood.

Adult↗

Immunological studies in patients with alcoholic liver disease: evidence for the in vivo activation of helper T cells and of the monocyte-macrophage system.

Immunologic parameters were evaluated in 22 patients with alcoholic liver disease (ALD). Patients with ALD had increased levels of circulating immune complexes (CIC) and serum immunoglobulins, particularly IgA. The classical complement pathway was preferentially activated in CIC-positive patients. There was no increase in total lymphocyte or total T lymphocyte counts, but a significant rise in both the helper/inducer population (OKT4) and helper/suppressor cell ratio (T4/T8) was noted. The presence of interleukin-2 receptors and HLA-DC/DS and HLA-DR antigens suggested in vivo activation of ALD patients' T cells. The rate of differentiation of B cells to plasma cells was high in both pokeweed mitogen-stimulated and unstimulated cultures of ALD patients' B cells, whereas plasma cell generation doubled when patient T lymphocytes were added to enriched normal B cells. The above data support a role for activated helper (T4+) T cells in the immune response initiated by alcoholic hepatitis. Serum angiotensin-converting enzyme levels and lysozyme levels were increased in ALD patients, and cultured adherent mononuclear cells from ALD patients secreted more lysozyme in vitro than normal cells, suggesting the presence of an activated monocyte-macrophage system in ALD.

Adult↗

Preliminary observation on the clinical tolerance of interferon-beta in cancer patients.

Nine patients with metastatic solid tumors were given IFN-beta by i.v. bolus injections. Six escalating doses (from 1 to 9 X 10(6) IU) followed by 6 additional injections at the dose of 9 X 10(6) IU were administered every other day (schedule A) in 3 of the 9 patients. IFN dose was also increased to a maximum of 46 X 10(6) IU, and 12 individual injections of 1, 2, 3.3, 5, 7, 9, 12, 16, 21, 27, 34 and 46 X 10(6) IU of IFN were given over a minimum of a 24-day period (schedule B) in 6 of the 9 patients. The single maximal tolerated dose ranged from 9 to 46 X 10(6) IU. The toxicity of IFN-beta given as scheduled in this study was significant but acceptable.

Adult↗

Immunorestorative properties of thymostimulin (TS) in patients with Hodgkin's disease in clinical remission.

Fifteen Hodgkin's disease patients (8 male, 7 female) aged 19-72 years, who had been in complete unmaintained remission for 1 year or more when the study was initiated, were given 50 mg thymostimulin (TS) IM daily for 60 consecutive days. When compared with 26-30 age- and sex-matched controls, as a group the patients' circulating ENR+, OKT+3, and OKT+4 cells were depressed (0.001 less than or equal to P less than or equal to 0.06), whereas their OKT+8 cell population was not. Low (greater than 1 SD or greater than 2 SD below mean in controls) or borderline (mean value of two subsequent tests greater than 1 SD below mean in controls) values of ENR+, OKT+3, and OKT+4 cells were seen in nine (group I) of the 15 patients tested, while the remaining six patients (group II) had normal T-cell proportions. Following TS treatment, the proportions of ENR+, OKT+3, and OKT+4 cells increased to normal in all group I patients. The T-cell levels, however, decreased to pretreatment values 60-70 days after completion of TS therapy. TS had no effect on the group II patients whose T-cell percentages had initially been normal. Spontaneous cell-mediated cytotoxicity (SCMC) was assessed in 11 patients, and irrespective of the baseline values, there was a significant enhancement (P less than 0.005) by day 15 of TS administration, which was maintained during treatment. SCMC, however, returned to pretreatment levels 60-70 days after TS was discontinued. The delayed skin test reactivity to DNCB was significantly depressed in all cases. Although TS restored the T-cell proportions, it failed to reverse DNCB reactivity from negative to positive in any of the patients tested. TS can thus restore defective T-cell frequencies and can enhance cytolytic functions that are potentially important in host immunosurveillance, but it apparently failed to improve the skin reactivity to neoantigen.

Adult↗

The differential diagnosis of hairy cell leukemia with a panel of monoclonal antibodies.

A panel of monoclonal antibodies reactive with normal human lymphoid cells and with hairy cells has been applied to the immunocytochemical analysis of hairy cell leukemia. Staining was performed by immunoenzymatic methods on frozen sections of bone marrow trephines and extramedullary tissues and on cell smears. Hairy cells reacted with antibodies against HLA-DR, leukocyte common antigen, B-cell antigens (antibodies To15 and B1) and with three anti-hairy cell monoclonal antibodies (S-HCL3, HC1, and HC2). Neoplastic cells in other B-cell lymphoproliferative disorders also expressed HLA-DR, leukocyte common, and B-cell antigens but were consistently negative for the antigen detected by monoclonal antibody S-HCL3. Furthermore, hairy cells differed from other neoplastic B-cells in that they were unreactive with monoclonal antibodies against C3b receptors, anti-Leu-1, Tü1, Tü33, and lacked a meshwork of dendritic reticulum cells. These findings establish a distinctive antigenic phenotype for hairy cell leukemia and indicate that it may be diagnosed reliably by immunoenzymatic labeling of tissue sections or cell smears.

Acute Disease↗

Chronic myelogenous leukemia.

Chronic myelocytic leukemia (CML) is a well-known myeloproliferative disorder, with typical clinical and hematological features, which develops into a lethal blastic crisis within an average of 4 years. In the last few years much has been learned about the cell responsible for the leukemic deviation, chromosomal abnormalities both in chronic phase and in blastic transformation, biochemical and cytochemical behavior of leukemic cells, and the immunology of the disease. On the contrary, polychemotherapy has brought but little progress in CML treatment. However, thorough research on prognostic factors at the onset of the disorder allows a more rational approach to the treatment, and in the near future interesting progress in bone marrow transplantation is to be expected. Also, monoclonal antibody techniques will reveal further knowledge on the origin and differentiation of leukemic cells and the relationship between the chronic phase and the blastic deviation.

Age Factors↗

A mature thymocyte-like phenotypic pattern on human cord circulating T-lymphoid cells.

Cord blood samples from healthy full-term newborns were tested with antimature and antiimmature lymphoid-cell monoclonal antibodies, as well as more traditional markers, in order to identify the phenotype of circulating precursor cells. The results demonstrated that human cord blood contains a lower number of OKT3+, E-rosetting mature T cells than adult blood, very high levels of OKT10+ cells, and few OKT9+, OKT8+ OKT3-, and OKT4+ OKT3- cells. Although the finding of OKT9+ and OKT10+ cord circulating cells could be indicative of cell activation, double marker studies in newborn blood pointed to phenotypically immature lymphoid subsets at different stages of maturation, according to Reinherz's hypothesis. In addition, the absence of nuclear Tdt-positive and hot-rosetting cells, together with the fact that most of these are OKT3+, OKT10+, OKT4+, or OKT8+ cells, suggests that the surface phenotype of newborn lymphocytes is similar to that of mature thymocytes.

Antibodies, Monoclonal↗

Intrapericardial tetracycline sclerosis in the treatment of malignant pericardial effusion: an analysis of thirty-three cases.

Thirty-three unselected patients with cardiac tamponade secondary to malignant pericardial effusion were treated by intrapericardial instillation of tetracycline hydrochloride. Complete control of the initial signs and symptoms of tamponade was obtained in 30 patients without concomitant chemotherapy or radiotherapy. The procedure did not result in clinically significant complications. Failure of the technique was related to premature removal of the catheter by the patient (one patient) or the inability to totally remove hemorrhagic, clot-filled pericardial fluid (two patients). Survival ranged between 28-704 days and extended survival was related to the performance status and/or chemoradiosensitivity of the primary cancer. No patient successfully treated subsequently developed recurrent cardiac tamponade or alternatively, constrictive pericarditis. Tetracycline pericardial instillation remains a safe, simple, and efficacious treatment of tamponade secondary to malignant disease.

Adult↗

5-Fluorouracil, vincristine and hydroxyurea combination chemotherapy in metastatic colorectal cancer.

Twenty consecutive patients who had biopsy proven metastatic colorectal cancer were treated with combination chemotherapy. The drug regimen (FVH), in a 4 week cycle, consisted of 5-fluorouracil (600 mg/m2 i.v. on days 1, 8, 15 and 22), vincristine (1.4 mg/m2 i.v. on day 4), and hydroxyurea (2400 mg/m2 p.o. on days 3, 10, 17 and 24). Three of the 18 evaluable patients achieved an objective tumor remission (2 CR and 1 PR) and 15 patients had stable disease. The overall response rate to FVH was therefore not superior to that achieved in patients who received 5-fluorouracil alone, and the overall survival in this study was comparable to that of other studies involving patients with metastatic colorectal cancer.

Antineoplastic Combined Chemotherapy Protocols↗

Humoral nonparathyroid hypercalcemia without evidence of bone involvement.

A case of humoral non-parathyroid hypercalcemia in a breast cancer patient is discussed. Bone metastases developed 23 months after the first clinical evidence of increased serum calcium levels and did not appear to be etiologically involved in this case of hypercalcemia. Serum levels of I-PTH and PGE2 were normal, as were urinary c-AMP levels. Furthermore, no significant response to corticosteroid therapy was observed. However, the correlation between the activity of metastatic disease and calcemia suggests that this cancer produced humoral factor(s) with calcium-mobilizing activity.

Adult↗

The in vivo effect of thymic factor (thymostimulin) administration on circulating immune complexes and serum lysozyme levels in untreated Hodgkin's disease patients.

The in vivo effect of a calf thymus extract, thymostimulin, on the levels of circulating immune complexes (CIC) and serum lysozyme was evaluated in 32 patients with untreated Hodgkin's disease. Using the platelet aggregation test for detecting CICs, 12 patients (37%) had positive titers before thymostimulin treatment; 3 patients (10%) remained positive following therapy. Serum levels of Clq-binding immune complexes were evaluated (greater than 24.5 micrograms/ml) in 8 patients prior to thymostimulin therapy (mean value: 42.3 micrograms/ml); 3 patients continued to have elevated levels after treatment. Serum lysozyme levels for Hodgkin's patients was similar to control values (10.6 vs. 8.3 micrograms/ml); however, the Hodgkin's patients with initially elevated CICs had a lower serum lysozyme level than patients with initially normal CICs (12.9 vs. 7.3, p less than 0.02). Thymostimulin increased serum lysozyme levels in the Hodgkin's patients in whom the CICs were initially elevated (7.3 vs. 10.4 micrograms/ml, p less than 0.05). These data suggest that thymostimulin exerts an effect on the nonspecific immune system of Hodgkin's disease patients.

Animals↗

Circulating immune complexes and serum lysozyme levels in untreated Hodgkin's disease. Their relationship to immune function.

Complement-fixing and non-complement-fixing circulating immune complexes were determined in 42 previously untreated Hodgkin's disease patients by Pl.A.T., C1qB-ELISA and KgB tests. The functional status of the monocyte-macrophage system was evaluated by measuring the serum lysozyme levels. These parameters were then correlated with the patient's immunocompetence, as assessed by the percentage of E-rosette forming cells and the PHA response. The Pl.A.T. was positive in 35.7% patients, the KgB-test in 34.3% and the C1qB-ELISA in 19%. There was overlapping of positive results in 37.5% patients. No correlation was found between CIC levels and stage, unfavourable histology or B symptoms. The PHA response was significantly depressed in CIC + patients, as detected by the C1qB-ELISA technique (p less than 0.0025). The data on serum lysozyme offer an insight into the possible mechanism regulating serum levels of CICs in Hodgkin's disease. Two distinct situations seem to exist: in the first, high CIC levels are associated with normal or low serum lysozyme values (p versus normal controls: n.s.); in the second, serum lysozyme levels are high and CIC absent (p less than 0.005 versus control values). The lowest lysozyme levels are also associated with a depressed lymphocyte PHA response. It could, therefore, be concluded that, in Hodgkin's disease, the presence, or absence, of CICs is directly correlated to the degree of monocyte-macrophage clearance activity and that the host's immunocompetence plays an important role in the induction and/or maintenance of this functional defect.

Antigen-Antibody Complex↗

Intracytoplasmic lysozyme in malignant hematologic disorders: an immunoperoxidase study.

Intracytoplasmic lysozyme was studied by the peroxidase antiperoxidase (PAP) and protein A-peroxidase methods in 130 cases of various myeloproliferative and lymphoproliferative disorders and 21 lymph nodes and bone marrow metastases from solid primary tumors. This marker, which can be identified in formalin or Zenker-fixed tissues, as well as in peripheral blood and bone marrow smears, proved useful to distinguish malignant myeloid and histiocytic tumors from malignant lymphoid and undifferentiated epithelial metastases. The diagnostic application of these findings are discussed.

Cytoplasm↗

Cell membrane markers and phytohemagglutinin reactivity of circulating lymphocytes from chronic myelocytic leukemia patients.

Lymphocytes from 22 patients with chronic myeloid leukemia (CML), 13 treated with polychemotherapy, eight by monochemotherapy, and one untreated, were analyzed for the presence of classic T and B cell surface markers (E-rosette, EAC-rosette, surface immunoglobulins) and for their ability to respond to phytohemagglutinin (PHA). The absolute number and percentage of E-rosetting cells (T-cells), EAC-rosetting cells and cells staining for surface immunoglobulins (B cells) were all significantly lower than controls (P less than or equal to 0.025). The response to PHA was also significantly lower in patients than in controls at the smaller concentrations of the mitogen (3.75 micrograms/ml, 30 micrograms/ml) tested (P less than or equal to 0.01); at a higher PHA concentration (120 micrograms/ml) the decrease in PHA stimulation approached significance (P = 0.07). These lymphocyte abnormalities support the concept that CML lymphocytes may be derived from the leukemic clone.

Adult↗