Overview of the First International Workshop to Define Swine Leukocyte Cluster of Differentiation (CD) Antigens.
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Animals↗
Biomedical subjects
A Bianchi
Publications and source records attributed to A Bianchi.
Autonomic changes during hypnosis: a heart rate variability power spectrum analysis as a marker of sympatho-vagal balance.
Spectral analysis of beat-to-beat variability in electrocardiography is a simple, noninvasive method to analyze sympatho-vagal interaction. The electrocardiogram is analyzed by means of an automatic, autoregressive modeling algorithm that provides a quantitative estimate of R-R interval variability by the computation of power spectral density. Two major peaks are recognizable in this specter: a low-frequency peak (LF, -0.1 Hz), related to the overall autonomic activity (ortho+parasympathetic) and a high-frequency peak (HF, -0.25 Hz), representative of the vagal activity. The LF/HF ratio is an index of the sympatho-vagal interaction. This technique was applied, using a computer-assisted electrocardiograph, to 10 healthy volunteers (6 high and 4 low hypnotizable subjects as determined by the Stanford Hypnotic Susceptibility Scale, Form C) in randomized awake and neutral hypnosis conditions. Preliminary results indicated that hypnosis affects heart rate variability, shifting the balance of the sympatho-vagal interaction toward an enhanced parasympathetic activity, concomitant with a reduction of the sympathetic tone. A positive correlation between hypnotic susceptibility and autonomic responsiveness during hypnosis was also found, with high hypnotizable subjects showing a trend toward a greater increase of vagal efferent activity than did low hypnotizables.
Adult↗
Correlation between disease activity and T-cell CD3 zeta chain expression in a B-cell lymphoma.
The T-cell receptor (TCR)/CD3 complex is the surface molecule responsible for the highly specific response to foreign antigens, including tumour-associated antigens. and correlations have been observed with disease status. Recently, low amounts of CD3 gamma and CD3 zeta chains in the CD3/TCR complex have been reported in long-term tumour-bearing mice as a possible mechanism for the impaired T-cell responses. In this study we report a B-cell lymphoma in which T-cell CD3 zeta expression correlated with disease activity.
CD3 Complex↗
Generation of anti-tumour activity by OKT3-stimulation in multiple myeloma: in vitro inhibition of autologous haemopoiesis.
T cells in multiple myeloma (MM) patients are highly susceptible to activation with the anti-CD3 monoclonal antibody (mAb) OKT3. When short-term OKT3 stimulation is carried out on bone marrow mononuclear cells (BMMC), large numbers of CD3+ CD25+ HLA-DR+ cells are rapidly generated and autologous malignant plasma cells are killed. OKT3 may thus be exploited in autologous bone marrow transplantation (ABMT) to purge residual plasma cells and simultaneously activate T cells to induce graft-versus-leukemia-like (GVL-like) activity upon reinfusion. However, the possible impact of ex-vivo short-term OKT3 stimulation on haematological recovery is unknown. The aim of this work was to investigate the effect of OKT3 stimulation in vitro on autologous haemopoietic progenitor cells (HPC) of MM patients. Colony formation by granulocyte-macrophage progenitor cells (granulocyte-macrophage colony-forming units, CFU-GM) was highly suppressed, although supernatants of OKT3-activated T cells contained up to 2,500 pg/ml of granulocyte-macrophage colony-stimulating factor (GM-CSF). T cell depletion completely prevented this suppression. Neutralizing antibodies against TNF-alpha, TNF-beta and IFN-gamma (which are also produced by OKT3-activated MM T cells) did not prevent it, and Transwell cultures showed that cell-to-cell contact was the main mechanism involved. OKT3-activated T cells also suppressed erythroid burst-forming units (BFU-E) and CFU-GM generation from HPC responsible for long-term maintenance of in vitro myelopoiesis. When tested on normal allogeneic BM, MM supernatants of OKT3-stimulated BMMC partially suppressed the generation of day 7 CFU-GM, but had no effect on day 14 CFU-GM. These data indicate that short-term stimulation of BMMC with OKT3 can be used to generate anti-tumour effector T cells for autologous adoptive immunotherapy. It is not a feasable approach for ex-vivo purging and activation procedures in ABMT because of its potent inhibition of autologous haemopoiesis.
Bone Marrow Cells↗
[Role of hepatitis C virus in the genesis of hepatic lesions observed in alcoholic patients with liver cirrhosis].
The aim of study was to assess the role of hepatitis C virus (HCV) infection in 164 alcoholic cirrhotic patients. We studied the prevalence of anti-HCV antibodies using ELISA and RIBA first and second generation tests. Twenty-two % of the patients had anti-HCV antibodies detected by ELISA 2, RIBA 2 test was positive in 10% of the patients and indeterminate in 3%. We compared epidemiological, biological and histological characteristics according to the results of the tests. By comparing ELISA 2-RIBA 2 positive patients to ELISA 2 negative patients, we observed, in the former, a) a higher serum aminotransferase activity, b) a lower serum gammaglutamyl transpeptidase activity, and c) a lower histological score of alcoholic hepatitis. In addition, in a group of ELISA 2 positive RIBA 2 negative patients, the values were intermediate between those of the two former groups. However, most of these patients had a negative third generation ELISA test. The whole results suggest that HCV is likely to play a role in the pathogenesis of liver damage in a high number of alcoholic cirrhotic patients.
Adult↗
Migration of acute lymphoblastic leukemia cells into human bone marrow stroma.
Most cases of acute lymphoblastic leukemia (ALL) arise from malignant transformation of B-cell precursors in the bone marrow. Recent studies have shown that normal and leukemic B-cell precursors bind to bone marrow stromal cells through the beta-1 integrins VLA-4 and VLA-5, thereby exposing early lymphoid cells to regulatory cytokines. It has been recently reported that the pre-B cell line NALM-6 is capable of migrating under layers of murine stromal cells in vitro (Miyake et al. J Cell Biol 1992;119:653-662). We have further analyzed leukemic cell motility using human bone marrow fibroblasts (BMF) as a stromal layer. The precursor-B ALL cell line NALM-6 rapidly adhered to BMF, and underwent migration or tunneling into BMF layers within 5 h, as demonstrated by light and electron microscopy, and confirmed by a chromium-labeling assay. Migration was also observed with the precursor-B ALL lines Reh and KM-3, with a T leukemia line RPMI-8402, the monocytic line U937, and the mature B line Daudi. In contrast, mature B (Raji), myeloid (K562, HL-60), and T lines (CCRF-CEM, MOLT-4) did not migrate. When cases of leukemia were analyzed, BMF migration was largely confined to precursor-B ALL, occurring in eight of 13 cases tested. Of other types of leukemia, migration was observed in one of four cases of T-ALL, but no evidence was seen in six acute myeloid leukemias and two patients with chronic lymphocytic leukemia. Only minimal migration into BMF was observed with purified sorted CD10+ CD19+ early B cells from normal adult marrow, while normal mature B lymphocytes from peripheral blood did not migrate. ALL migration was inhibited by monoclonal antibodies to the beta sub-unit of the VLA integrin family, and by a combination of antibodies to VLA-4 and VLA-5. Partial inhibition was also observed when leukemic cells were incubated with antibodies to VLA-4, VLA-5, or VLA-6 alone. In contrast, treatment of stromal cells with antibodies to vascular cell adhesion molecule or fibronectin (ligands of VLA-4 and VLA-5) did not prevent leukemic cell migration. These results indicate that ALL cells are highly motile and capable of rapid migration within marrow stroma, an effect largely mediated by VLA-4 and VLA-5. In the case of precursor-B ALL, this process may reflect a homing mechanism to areas of selective growth advantage within the bone marrow microenvironment.
Antigens, CD↗
[Preoperative cytodiagnosis by needle aspiration of follicular thyroid lesions].
In the period 1989-92, 2729 F.N.A.B. were performed: 585 with an histological control were reviewed. The aim of the study was to evaluate the risk of carcinomatous occurrence in the follicular-structured smears and to suggest a new cytodiagnostic classification. Out of 398 follicular-structured smears, 188 were colloid nodules (CN), 38 thyreocytic hyperplasias without nuclear atypia (THWNA), 146 predominantly follicular lesions (PFL), 26 follicular lesions with nuclear pleomorphism (FLWNP). The last one showed a high incidence of neoplasia (69.2%) and carcinoma (46.1%); the second and the third only a difference in the incidence of benign neoplasms (32.9 vs. 15.8%), with almost the same percentage of occurrence of malignancies (2.6 vs. 2.1%). Such results suggest that a six-months dilatory strategy might be useful in simple follicular lesions (THWNA and PFL) whereas a cytological follicular pattern with nuclear pleomorphism requires a surgical treatment for the high risk of carcinomatous occurrence.
Biomarkers, Tumor↗
[Mesenteric ischemia diagnosed with Doppler ultrasonography and successfully treated with intra-arterial urokinase].
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Aged↗
[The infusion of calcium gluconate in coronary disease patients induces myocardial ischemia via a possible adenosine-mediated mechanism].
In the first part of the study 5 control subjects were submitted to iv infusion of 0.2 mM/kg of calcium gluconate in 20 min. Total calcium (atomic absorbtion method), ionized calcium (ion-selective electrode method) and adenosine (HPLC technique) were measured at the following times: 0 (baseline), 5, 10, 15, 20 (end of infusion), 25, 30, 35, and 50 min. The increase of total and ionized calcium serum levels was associated with a significant increase of adenosine plasma levels (from 207 +/- 41 to 362 +/- 63 nM, p < 0.001). Since the increase of adenosine plasma levels, obtained either with adenosine or dipyridamole (an adenosine reuptake inhibitor), has been used to test the coronary reserve in patients with coronary artery disease (CAD), in the second part of the study we compared the effects of calcium infusion with dipyridamole in 15 CAD subjects. Pharmacological stress tests were evaluated by monitoring two-dimensional echocardiography, ECG, heart rate, blood pressure and rate-pressure product. Ten patients were positive both to dipyridamole stress test and to calcium infusion, ad demonstrated by the onset of new areas of transient asynergy in the same myocardial regions. Dipyridamole infusion determined a significant increase in heart rate and rate pressure-product in all patients (both in positive and in negative), whereas calcium induced a slight, not significant decrease of these parameters.(ABSTRACT TRUNCATED AT 250 WORDS)
Adenosine↗
[Changes in the cellular proliferation of the healthy mucosa in patients with colorectal cancer].
AIM: To analyze differences in the proliferative pattern of normal mucosa between patients with colorectal cancer and healthy subjects. PATIENTS AND METHODS: By using flow cytometry we examined the proliferative pattern (Proliferative Index and S-Phase) in samples of normal mucosa from 34 patients operated on for colorectal cancer at our hospital and from 14 healthy subjects as a control group. RESULTS: All examined samples were diploid. The Proliferative Index and S-Phase in the Cancer Group were significantly higher than in the Control Group (16.7 +/- 5.9 vs 11.4 +/- 4, p < 0.003, and 11.9 +/- 3.9 us 6.6 +/- 3 p < 0.0004). CONCLUSIONS: These findings provide evidence for an altered proliferative pattern in the healthy colonic mucosa of patients with colorectal cancer.
Adult↗
[Cholelithiasis after total gastrectomy for gastric cancer].
AIM: To examine the incidence of cholelithiasis in patients after total gastrectomy for gastric cancer. PATIENTS AND METHODS: Patients operated for gastric cancer at our hospital were retrospectively studied. Criteria to be included in the study were: 1) Follow-up of more than 3 years, 2) Cholelithiasis excluded preoperatively by ultrasonography, 3) Ultrasonographic postoperative control once a year. RESULTS: Ten patients met the established criteria. Six of them developed biliary lithiasis, and four of them needed surgical treatment for biliary symptomatology. CONCLUSIONS: The incidence of cholelithiasis after total gastrectomy for gastric cancer is high, and surgical treatment is often necessary. However our data does not support prophylactic cholecystectomy in the course of total gastrectomy.
Adult↗
Analysis of the mechanism of adhesion of precursor-B acute lymphoblastic leukemia cells to bone marrow fibroblasts.
Normal B lymphopoiesis is dependent on a close relationship between B-cell precursors and the bone marrow (BM) microenvironment. To further understand the mechanisms regulating the proliferation of the malignant counterpart of B-cell precursors, namely precursor-B acute lymphoblastic leukemia (ALL), we examined the adhesion to BM fibroblasts (BMF) of 19 cases of precursor-B ALL using a chromium labeling assay. Eleven of 19 cases showed greater than 10% binding to BMF (range 2.3% to 54.8%, mean 19.1%). Binding was increased approximately twofold by preincubation of BMF with tumor necrosis factor and interleukin-4, which also resulted in upregulation of expression of vascular cell adhesion molecule-1 (VCAM-1) on BMF. The mechanism of attachment was investigated using murine monoclonal antibodies to leukocyte integrins, principally the beta, integrins VLA-4 and VLA-5, which were demonstrated to be present on most cases by flow cytometry. Statistically significant inhibition of adhesion was observed with antibodies to the beta 1 common subunit, VLA-4, and VLA-5, whereas little effect was seen with antibodies to VLA-6 or the beta 2 integrin subunit. Preincubation of fibroblasts with an antibody to VCAM-1 (a ligand of VLA-4) inhibited leukemic cell binding in the majority of cases, which was an effect also observed on cytokine-stimulated BMF. However, a minority of cases, as well as the pre-B lines NALM-6 and KM-3, showed no evidence of inhibition of adhesion with anti-VCAM-1 antibodies. Treatment of BMF with antifibronectin antibody alone had little effect on ALL adhesion and did not enhance the inhibitory effect of anti-VCAM-1. These data indicate that precursor-B ALL cells bind to BM stroma through the beta 1 integrins VLA-4 and VLA-5 and that this effect is partly mediated by VCAM-1 on stromal cells, although other undefined VLA ligands are also likely to be involved. Attachment of ALL cells to stroma is likely to play a key role in regulating the survival and growth of these cells through exposure to stromal cytokines.
Adolescent↗
Co-stimulatory signal delivered by CD73 molecule to human CD45RAhiCD45ROlo (naive) CD8+ T lymphocytes.
CD73 is a molecule expressed by a subset of CD8+ human T lymphocytes and is involved in T cell activation. CD73 expression and function were analyzed in peripheral blood CD45RAhiCD45ROlo (naive) and CD45RAloCD45ROhi (memory) CD8+ cells. We found that CD73 was expressed by a majority of naive cells (74 +/- 12%), whereas fewer memory cells were CD73+ (29 +/- 10%). Moreover, CD73 was selectively expressed by the CD11b- subset of naive CD8+ cells, which were almost all CD73+. The same result was found on CD8+ cord blood lymphocytes, which prevalently display the naive phenotype. Naive CD8+ CD11b- cells were almost unresponsive to CD3 engagement, but this apparent anergy was completely overcome when CD3 and CD73 were simultaneously cross-linked by plastic-immobilized CD73 and CD3 mAb, showing that CD73 delivers an accessory signal that allows their activation via the CD3/TCR. This costimulatory signal was tenfold more potent than that induced by CD28 ligation. A phosphotyrosine analysis by Western blotting showed that cross-linking of CD73 induced the phosphorylation of two proteins with a molecular mass of approximately 28 and 100 kDa respectively, whereas ligation of CD3 induced phosphorylation of many substrates. When CD3 and CD73 were simultaneously triggered these substrates were hypophosphorylated. Because CD73 is linked to the cell surface by a GPI anchor, the transduction of this signal is probably mediated by a lateral interaction with transmembrane molecules. This hypothesis was assessed by cocapping, which showed that CD73 associates strongly with CD45RC, moderately with CD8, and weakly with CD3. These data suggest that CD73 signaling is coupled to both tyrosine kinase and phosphatase activities.
5'-Nucleotidase↗
Rapid generation of antiplasma cell activity in the bone marrow of myeloma patients by CD3-activated T cells.
We have recently shown that peripheral blood T cells of multiple myeloma (MM) patients are very susceptible to stimulation of the T-cell receptor/CD3 complex with anti-CD3 monoclonal antibodies (MoAbs). CD3 stimulation is currently under clinical investigation as a nonspecific approach to boost antitumor effector mechanisms. The aim of this study was to determine whether the hyperreactivity of MM T cells to CD3 stimulation could be exploited to generate antitumor activity. Bone marrow mononuclear cells (BMMCs) from 65 MM patients were stimulated with the anti-CD3 MoAb OKT3 and the effect of this stimulation on autologous T cells and plasma cells was evaluated. The number of CD3+ CD25+ cells on day 6 was significantly higher in MM than the controls (30 normal individuals) (P = .001). Kinetic studies showed that 3H-thymidine incorporation peaked on day 3 and that the T-cell expansion peaked on days 5 and 6. In MM, T-cell activation markedly affected the survival of autologous plasma cells; their number in OKT3-treated cultures was significantly lower than in unstimulated cultures (P < .0001). T-cell activation and plasma cell decrease were not observed when T cells were removed from BMMC preparations. MM produced significantly higher levels of interferon-gamma (P = .005) and tumor necrosis factor-beta (P = .001), but lower levels of tumor necrosis factor-alpha (P < .001) than normal individuals. Interferon-gamma only was partially involved in CD3-induced plasma cell killing. Transwell cultures showed that the main mechanism by which CD3+ CD25+ cells affected plasma cells was direct cell-to-cell contact rather than cytokines. In conclusion, T cells in MM BMMCs possess distinct features in terms of susceptibility to CD3 stimulation and cytokine production compared with normal bone marrow T cells that can be exploited to generate antiplasma cell activity.
Antibodies, Monoclonal↗
Brain acetyl-CoA carboxylase: isozymic identification and studies of its regulation during development and altered nutrition.
Acetyl-CoA carboxylase, the rate-limiting enzyme of fatty acid synthesis, exists as an oligodendrocyte-associated enzyme in brain and plays an important role in supplying fatty acid for myelination. Rat brain acetyl-CoA carboxylase (ACC) has been identified as a single isozyme of M(r) = 265,000 daltons, indistinguishable immunologically from the isozyme in rat adipose tissue and liver. Total activity of brain ACC declines from birth to 4 weeks of age in the newborn rat. This change in activity can entirely be accounted for by changes in enzyme content, not enzyme specific activity, and is paralleled by decreases in ACC mRNA. In contrast, cardiac, skeletal muscle and liver ACC does not change in content over this developmental period. Unlike ACC in liver and adipose tissue, the enzyme content and specific activity of brain ACC is invariant during various states of nutrition. These data indicate that the brain ACC is subject to unique regulation, as compared to non-neural enzyme. The mechanisms underlying the control of neural ACC activity may be important to understanding the process of myelination during development and to a more general understanding of the factors regulating ACC expression/activity in other tissues.
Acetyl-CoA Carboxylase↗
Preventing congenital abnormalities.
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Abortion, Induced↗
Fever and granulocytopenia in children with cancer: a study of 299 episodes with two treatment protocols in Brazil.
In Brazil, 226 children with cancer presenting 299 episodes of fever and neutropenia (< or = 500/mm3) were treated with two consecutive empirical regimens. Regimen I-Cefoxitin Amikacin-Carbenicillin; and Regimen II Ceftriaxone-Amikacin. 67.0% of the patients had leukemias or lymphomas, documented infections occurred in 47.2%, superinfections occurred in 18.7% (Reg. I) and 17.8% (Reg. II) of the episodes. The most common agents identified in Reg. I and Reg. II were, respectively, Gram negative rods (55.0%) and Gram positive cocci (52.6%). The overall rate of success with modifications (Amphotericin B, Vancomycin, Clindamycin, Metronidazole) was higher in Reg. II (93.0%) than in Reg. I (84.0%). This study shows that the appropriate formula to maximize the successful treatment of children with cancer, fever and neutropenia in developing nations includes adherence to established principles of supportive care, utilizing the optimal antibiotic agents available in the country. It is important to promote the necessary modifications along the treatment having in mind the high index of resistant agents.
Adolescent↗
Association of malignancy and Langerhans' cell histiocytosis: report of three cases.
Among 44 children with Langerhans' cell histiocytosis (LCH) seen at the Pediatric Department of the A.C. Camargo Hospital, São Paulo, Brazil, three developed malignancy, two before and one after the diagnosis of LCH. Malignancy could be attributed to treatment in one of the three children. Whether the cancer in the other two children represents a chance association of the two processes or is treatment-related, is unknown.
Child↗