Quality of life issues in patients with osteoporotic fractures.
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Aged↗
Biomedical subjects
C Grossi
Publications and source records attributed to C Grossi.
Role of Helicobacter pylori serology in atrophic body gastritis after eradication treatment.
BACKGROUND: It has been reported that 50% of patients with atrophic body gastritis have positive Helicobacter pylori antibody titres only. In atrophic body gastritis, a decrease in H. pylori antibodies after eradication treatment has been reported, suggesting that serology may indicate an active H. pylori infection. AIM: To investigate the time course of H. pylori antibodies and gastric inflammation after eradication treatment in patients with atrophic body gastritis, and to determine whether serology alone can be considered as a valid tool to assess the efficacy of eradication treatment in patients with atrophic body gastritis. METHODS: Twenty-seven patients with atrophic body gastritis (12 serologically H. pylori-positive only, ABG-S+; 15 H. pylori-positive at histology and serology, ABG-H+) were included in the treatment group, and 17 patients (all ABG-S+) in the no treatment group. All patients had gastroscopy plus biopsies evaluated according to the updated Sydney system and H. pylori immunoglobulin G determination: in the treatment group, at baseline and 6 and 24 months after eradication (bismuth-based triple regimens); in the no treatment group, at baseline and after 3 years. RESULTS: In the treatment group, in ABG-S+ patients, H. pylori antibodies decreased significantly 6 months after treatment [37.5 U/mL (16-100 U/mL) vs. 15 U/mL (0--100 U/mL), P < 0.01], but 2 years after treatment no further decrease occurred. In addition, in ABG-H+ patients, a significant decrease in H. pylori antibodies occurred 6 months after treatment [45 U/mL (12.5-100 U/mL) vs. 31 U/mL (0-65 U/mL), P < 0.01], but a further decrease was also observed 2 years after treatment [20 U/mL (0-56 U/mL), P < 0.01]. In ABG-S+ patients, no correlation was observed between the H. pylori antibodies and gastric inflammation score, whereas, in the ABG-H+ group, this correlation was extremely significant (r=0.5991, P < 0.0001). In the no treatment group, at follow-up, a significant decrease in H. pylori antibodies was observed [26 U/mL (15-100 U/mL) vs. 22 U/mL (0-53 U/mL), P < 0.05], but the gastric body inflammation remained unchanged. CONCLUSIONS: This study shows that, in ABG-S+ patients after eradication treatment, serology does not keep in step with gastric inflammation. This suggests that, in patients with atrophic body gastritis, serology alone may not be valid for the assessment of the efficacy of eradication treatment.
Acute Disease↗
Two-thirds of atrophic body gastritis patients have evidence of Helicobacter pylori infection.
BACKGROUND: Helicobacter pylori is involved in the induction of atrophic body gastritis (ABG). During the progression of atrophic gastritis the disappearance of H. pylori has been documented and in time serology is the only sign that indicates a previous infection. It has been shown that a positive serology, in ABG patients without histological evidence of infection, indicates an active H. pylori infection. AIM: To investigate in a population of patients with ABG the prevalence of H. pylori infection on the basis of histology and serology. PATIENTS: A total of 150 consecutive outpatients with atrophic body gastritis were diagnosed on the basis of a screening system. METHODS: All patients had a detailed assessment including measurement of specific anti-H. pylori antibodies, parietal cell antibodies, and fasting gastrin, gastroscopy with biopsies from gastric antrum and body. RESULTS: 24.6% of patients were histologically and serologically negative (Group A). 52.7% H. pylori was not detected on histology but IgG to H. pylori were in all these patients elevated (Group B). 22.6% of patients were found to be positive at histology in the corpus mucosa; all but one of these patients had elevated circulating IgG to H. pylori (Group C). Mean corporal atrophy score in Group B patients was statistically lower than in Group A patients (2.43 +/- 0.08 vs. 2.75 +/- 0.09; p <.05), but was statistically higher than in Group C patients (1.79 +/- 0.11; p <.001). Thus, in corporal mucosa a gradient of atrophy was shown: Group C < Group B < Group A. A similar gradient was observed for the presence of pernicious anemia being lowest in Group C 11.8% increasing to 45.6% in Group B and being highest in Group C 75.6%. A statistical correlation was obtained (r =.04791, p <.05) between the histological score of corporal atrophy and the titer of antibodies to parietal cells and an inverse correlation was obtained (r = -.2322, p <.0001) between the histological score of corporal atrophy and IgG to H. pylori. CONCLUSION: This study shows that two-thirds of ABG patients have evidence of H. pylori infection. This suggests that atrophic gastritis of the corpus is a spectrum of damage where H. pylori is a key agent able to induce gastric atrophic damage and also gastric autoimmunity.
Adult↗
Signaling through CD38 induces NK cell activation.
Human CD38 is a signal transduction molecule, and, concurrently, an ectoenzyme catalyzing the synthesis and degradation of cyclic ADP-ribose (cADPR), a potent Ca2+ mobilizer. One facet of CD38 that has not yet been addressed is its role in NK cells. To this end, the events triggered by CD38 ligation with agonistic mAb were analyzed on freshly purified human NK cells. Ligation was followed by (i) a significant rise in the intracellular level of Ca2+, (ii) increased expression of HLA class II and CD25, and (iii) tyrosine phosphorylation of discrete cytoplasmic substrates. The phosphorylation cascade involved CD3-zeta and FcepsilonRIgamma chains, zeta-associated protein (ZAP)-70 and the proto-oncogene product c-Cbl. NK effector functions were then analyzed: CD38 signaling was able (iv) to induce release of IFN-gamma and, more prominently, of granulocyte macrophage colony stimulating factor, as assessed by measuring both mRNA and protein products; and, lastly, (v) to induce cytolytic effector functions on target cells after IL-2 activation, as shown both by cytotoxicity assays and ultrastructural changes. The tyrosine-phosphorylated substrates and all the effects mediated by CD38 were similar to those observed following triggering via CD16 (FcgammaRIIIA); moreover, Ca2+ mobilization via CD38 no longer operated in NK-derived cell lines lacking CD16. These results suggest that the activation signals transduced by CD38 in NK cells elicit relevant cellular events. The effects are similar to those elicited via CD16 and possibly rely on common signaling pathways.
ADP-ribosyl Cyclase↗
Comparison between single and double internal mammary artery grafts: results over ten years.
BACKGROUND: In view of the superior patency of the internal mammary artery (IMA), grafting of this vessel to the left anterior descending artery is advantageous in terms of survival and quality of life; the benefits of using both the mammary arteries remain unproved. METHODS: Among the patients operated upon during the period 1988-1990, we randomly selected 150 patients in whom one IMA (group 1) was grafted and 150 patients in whom both IMAs (group 2) were grafted. The survival and event free curves of these two groups of patients were designed using the Kaplan-Mayer method; the log-rank test was used to assess the statistical difference between the curves and to determine whether, in the long term, benefits were superior in patients in whom both IMAs were grafted. RESULTS: Patients in group 1 were older (p = 0.002). In this group there were more patients with diabetes (p = 0.004) and with peripheral vascular disease (p = 0.047). There were more female patients in group 2 (p < 0.02) and more coronary vessels were grafted (p = 0.03). Follow-up was complete (100%) and equivalent in duration for both groups (109 +/- 30 months for group 1 and 110 +/- 33 months for group 2, p = NS). The survival rate at 10 years was equal for both groups (82.5 +/- 3.4% for group 2 vs 82.9 +/- 3.2% for group 1, p = NS) and so was the freedom from cardiac death. The provocative test for myocardial ischemia was more frequently positive in group 1 than in group 2 (21 vs 10 cases, p = 0.054). Freedom from new myocardial infarction (p = NS), angina recurrence (p = NS) and reoperation (p = NS) was equally distributed during follow-up. Group 2 patients more frequently necessitated coronary angioplasty but the difference was not significant (p = 0.17). Survival free from angina recurrence, new myocardial infarction, coronary angioplasty and reoperation was more frequent in group 2 (respectively 74.6 +/- 3.8 vs 70.7 +/- 4.1%) but the difference was not statistically significant (p = NS). CONCLUSIONS: After 12 years of follow-up, patients submitted to grafting of a single IMA more frequently presented with inducible myocardial ischemia, but neither survival nor the quality of life were superior in the patients in whom both IMAs were grafted.
Aged↗
[Surgical repair of degenerative atrial valve: long-term results].
BACKGROUND: The advantages of mitral valve repair in myxomatous regurgitation are well established. The durability of this reconstructive procedure is variable. The timing of operation is the surgeon dilemma. The aim of this study was to evaluate the early and long-term results of mitral valve repair in myxomatous regurgitation. METHODS: Between January 1990 and December 1997, 121 patients (77 males, 44 females) were operated on for myxomatous regurgitation with mitral valve repair. The surgical indication was based on the severity of mitral valve insufficiency and left ventricular dysfunction rather than the functional class. The surgical techniques were: quadrangular resection of the posterior mitral leaflet and sliding suture, triangular resection of the anterior mitral leaflet, chordal transposition and neo-chords suture, prosthetic ring (Carpentier-Edwards and Biflex rings) suture. RESULTS: There was 1 hospital death (0.8%). Long-term follow-up between 6 months and 107 months was available in 100% surviving patients. There were 6 late deaths, 3 for cardiac and 3 for non-cardiac events. CONCLUSIONS: Valve repair in mitral regurgitation caused by myxomatous disease provides excellent survival results at 51 months. Adverse outcome occurs in patients with preoperative left ventricular dysfunction, even if asymptomatic.
Adult↗
Iron deficiency anaemia and Helicobacter pylori infection.
Iron deficiency anaemia (IDA) is the most common form of anaemia world-wide. IDA is the simple result of an imbalance between iron loss and absorption. Gastric function with hydrochloric and ascorbic acid is essential for iron absorption. Some strains of Helicobacter pylori are able to acquire iron, competing with the host. A large percentage of patients with atrophic body gastritis (ABG) develop IDA and 61% of them are H. pylori positive. Recent evidence suggests that H. pylori infection could cause IDA in the absence of peptic ulcer or other upper gastrointestinal (GI) tract bleeding lesions. Gastritis extending to the corpus and a high bacterial load are features of these patients. About 70% of IDA patients with ABG or H. pylori gastritis are premenopausal women. Both ABG and H. pylori gastritis should be considered when evaluating the GI tract of patients with iron deficiency anaemia.
Absorption↗
Role of Helicobacter pylori infection in pernicious anaemia.
BACKGROUND: Pernicious anaemia is associated with atrophic body gastritis and considered an autoimmune disease. Whether Helicobacter pylori is involved in the induction of pernicious anaemia is uncertain. AIMS: To investigate the prevalence of Helicobacter pylori infection in pernicious anaemia patients and to ascertain whether the Helicobacter pylori-positive patients had distinctive clinical and gastric morphofunctional characteristics. PATIENTS AND METHODS: A series of 81 consecutive pernicious anaemia patients underwent serological, functional and endoscopic/histological investigations. RESULTS: A total of 49 (60.5%) patients were Helicobacter pylori-positive (males 61.2% vs females 38.8%). No difference was observed in clinical and morphofunctional characteristics between Helicobacter pylori-positive and negative patients, whereas distinctive functional/histological features between histologically Helicobacter pylori-positive (n=8) and serologically Helicobacter pylori-positive (n=41) cases were detected. In the histologically Helicobacter pylori-positive group, Pepsinogen I was higher [13 (058) vs 5 (0-26) ng/ml; p=0.0025)] and positivity for anti-parietal cell antibodies was lower [42.9% vs 76.9, p=0.0867]. Antral histological variables of the gastritis score were significantly higher in the histologically Helicobacter pylori-positive than in the serologically Helicobacter pylori-positive patients, but this latter group had a higher score of body atrophy (2.63+/-0.12 vs 1.71+/-0.29; p=0.0051). Body inflammation was also significantly higher in the histologically Helicobacter pylori-positive group (chronic inflammation: 1.43+/-0.2 vs 1.05+/-0.06; p=0.0271; inflammation acitivity: 0. 57+/-0.3 vs 0.15+/-0.06, p=0.0220). Antral mucosa was normal in 24/41 (58.5%) of the serologically Helicobacter pylori-positive patients, but only in 1/8 (12.5%) of the histologically Helicobacter pylori-positive patients (p=0.0232). CONCLUSIONS: Almost two thirds of pernicious anaemia patients have evidence of Helicobacter pylori, but only those with an active Helicobacter pylori infection have distinctive functional and histological features. These findings support the hypothesis that Helicobacter pylori infection could play a triggering role in a subgroup of pernicious anaemia patients.
Adult↗
Hypersecretory duodenal ulcer and Helicobacter pylori infection: a four-year follow-up study.
BACKGROUND: About 10% of duodenal ulcer patients are characterized by gastric acid hypersecretion with normal gastrin values. Relapsing duodenal ulcer after Helicobacter pylori cure has been related to high acid output and maintenance antisecretory therapy has been suggested in hypersecretory duodenal ulcer patients. The role of Helicobacter pylori infection and the effects of Helicobacter pylori cure in hypersecretory duodenal ulcer patients still remain to be fully studied. AIM: To study: a) whether gastric acid hypersecretion "per se" is a risk factor for duodenal ulcer recurrence; b) whether maintenance antisecretory therapy is necessary after eradication in hypersecretory duodenal ulcer patients. PATIENTS: The study population comprised 8 hypersecretory duodenal ulcer patients, selected from a population of 79 Helicobacter pylori-positive duodenal ulcer patients. METHODS: Hypersecretory duodenal ulcer patients were followed-up for at least 4 years after eradication. Gastric acid secretion was measured again 12 months after Helicobacter pylori eradication. Gastroscopy with histology was performed 3, 6, 12 and 36 months after treatment, 13C-urea breath test after 42 months; clinical questionnaires were completed every 6 months. RESULTS: After eradication, despite a not significantly reduced high acid output (median value of basal acid output and pentagastrin-stimulated acid output, respectively, 23.1 mEq/h and 64.1 mEq/h before treatment vs 16 mEq/h and 49.7 mEq/h 12 months after treatment), all patients were free from symptoms, none of them had duodenal ulcer relapse or complications (7/8 before treatment), or needed antisecretory maintenance therapy, except for one patient taking non-steroidal anti-inflammatory drugs. CONCLUSIONS: These findings, obtained in a selected population of hypersecretory duodenal ulcer patients with long-term follow-up, suggest that after successful Helicobacter pylori eradication gastric acid hypersecretion "per se" is not able to determine the recurrence of duodenal ulcer.
Adolescent↗
Effect of high-flux dialysis on the anaemia of haemodialysis patients.
BACKGROUND: Anaemia is one of the major clinical characteristics of patients with chronic renal failure, and has a considerable effect on morbidity and mortality. Adequate dialysis is of paramount importance in correcting anaemia by removing small and medium-sized molecules, which may inhibit erythropoiesis. However, high-molecular-weight inhibitors cleared only by means of highly porous membranes have also been found in uraemic serum and it has been claimed from uncontrolled studies that high-flux dialysis could improve anaemia in haemodialysis patients. METHODS: We therefore planned this multicentre randomized controlled trial with the aim of testing whether the use of a large-pore biocompatible membrane for a fixed 12-week follow-up improves anaemia in haemodialysis patients in comparison with the use of a conventional cellulose membrane. Eighty-four (5.3%) of a total of 1576 adult haemodialysed patients attending 13 Dialysis Units fulfilled the entry criteria and were randomly assigned to the experimental treatment (42 patients) or conventional treatment (42 patients). RESULTS: Haemoglobin levels increased non-significantly from 9.5+/-0.8 to 9.8+/-1.3 g/dl (dP=0. 069) in the population as a whole, with no significant difference between the two groups (P:=0.485). Erythropoietin therapy was given to 32/39 patients (82%) in the conventional group, and 26/35 (74%) in the experimental group (P:=0.783) with subcutaneous administration to 26/32 patients in conventional and to 23/26 patients in experimental group, P:=0.495. Dialysis dose (Kt/V) remained constant in both groups (from 1.30+/-0.17 to 1.33+/-0.20 in the conventional group and from 1.28+/-0.26 to 1.26+/-0.21 in the experimental group, P:=0.242). Median pre- and post-dialysis beta(2)-microglobulin levels remained constant in the conventional group (31.9 and 34.1 mg/dl at baseline) and decreased in the experimental group (pre-dialysis values from 31.1 to 24.7 mg/dl, P:=0.004 and post-dialysis values from 24.8 to 20.8 mg/dl, P:=0.002). Median erythropoietin doses were not different at baseline (70 IU/kg/week in conventional treatment and 90 IU/kg/week in experimental treatment, P:=0.628) and remained constant during follow-up (from 70 to 69 IU/kg/week in the conventional group and from 90 to 91 IU/kg/week in the experimental group, P:=0.410). Median erythropoietin plasma levels were in the normal range and remained constant (from 12.1 to 12.9 mU/ml in the conventional group and from 13.2 to 14.0 mU/ml in the experimental group, P:=0.550). CONCLUSIONS: This study showed no difference in haemoglobin level increase between patients treated for 3 months with a high-flux biocompatible membrane in comparison with those treated with a standard membrane. When patients are highly selected, adequately dialysed, and have no iron or vitamin depletion, the effect of a high-flux membrane is much less than might be expected from the results of uncontrolled studies.
Aged↗
Edge-to-edge repair of congenital familiar tricuspid regurgitation: case report.
We report a case of edge-to-edge (Alfieri's technique) repair of congenital familiar tricuspid regurgitation in a 49-year-old woman, who had severe tricuspid regurgitation, atrial septal defect with left-to-right shunt, and two stenoses in peripheral branches of the left pulmonary artery, of no clinical relevance. The repair was performed through a longitudinal inferior partial sternotomy. The atrial septal defect was closed by direct suture; the anterior and posterior leaflets of the tricuspid valve were sutured together. The chordae to the prolapsing medial part of the anterior leaflet were shortened by direct suture to the leaflet free edge. Annuloplasty was performed by means of a Carpentier ring. The final step was edge-to-edge approximation of the septal leaflet to the new antero-posterior position with two interrupted stitches. The hemodynamic result was excellent, and the patient eventually returned to full active life.
Cardiac Surgical Procedures↗
Changes in adhesion molecule expression on lymphoblasts during acute lymphoblastic leukemia treatment.
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Antineoplastic Agents, Hormonal↗
Prevalence and causes of hypergastrinemia in primary hyperparathyroidism: a prospective study.
Gastrin levels have been reported to be often increased in patients with primary hyperparathyroidism (PHPT) considered to be caused by hypercalcemia. To determine the prevalence of increased basal gastrin and to investigate its causes, 52 consecutive patients with PHPT were studied prospectively, undergoing a clinical, biochemical, and gastric morphofunctional assessment before any parathyroid surgical procedure. This included evaluation of basal and secretin-stimulated gastrin, basal and pentagastrin-stimulated gastric acid secretion, upper gastrointestinal endoscopy, with histological evaluation for gastritis and Helicobacter pylori infection. Twenty of the 52 PHPT patients (38.5%) had increased fasting gastrin. Further investigation allowed us to clearly demonstrate the causes of hypergastrinemia in 16 of these 20 patients. In 7 of 20 (35%), hypergastrinemia was caused by gastric fundus atrophy; in 3 patients (15%), Zollinger-Ellison syndrome with Multiple Endocrine Neoplasia type I was diagnosed; whereas in another 20% of patients, mild hypergastrinemia was ascribed to Helicobacter pylori gastritis. Finally, in 2 patients, additional clinical history revealed an occasional use of the gastric antisecretory drug omeprazole a few days before the serum gastrin determination. This study shows that the hypercalcemic status per se is not sufficient to produce an increase in fasting gastrin levels. Furthermore, gastric fundus atrophy, and not gastrinoma, is the major cause of relevant (>160 pg/mL) hypergastrinemia.
Adult↗
Images in nephrology. Vascular catheter apparently well-placed.
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Aged↗
[The use of bilateral mammary artery in myocardial revascularization. The risk factors emergent from a multivariate analysis conducted on 474 patients].
BACKGROUND: The internal mammary artery is used as coronary artery graft conduit because of its superior patency. According to some authors, the bilateral IMA can increase perioperative morbidity. The aim of this study was to determine the risk factors increasing perioperative mortality and morbidity in the use of bilateral IMA. METHODS: We analyzed the data of 474 patients operated consecutively with the use of bilateral IMA between January 1987 and December 1995 at the Department of Cardiac Surgery of the Varese Hospital. The univariate analysis was done on 17 ordinal variables using a "Fisher exact test" and on 4 continuous variables by "pooled-variance t-test" to investigate risk factors for mortality, mediastinitis, superficial wound infection and aseptic dehiscence of the sternum; a p-value lower than 0.1 was used as cut-off point to introduce the variables into a stepwise multiple logistic regression analysis. RESULTS: From the univariate analysis are: postoperative low-output syndrome (p = 0.01), LVEF (p = 0.02) and number of grafts (p = 0.04) are correlated to hospital mortality (1.5%); obesity (p < 0.001) and peripheral arteriopathy (p = 0.009) are correlated to postoperative mediastinitis (5%); obesity (p < 0.001), peripheral arteriopathy (p = 0.009), surgeon (p = 0.001), year of operation (p < 0.001), reoperation for bleeding (p = 0.004) and length of extracorporeal circulation (p = 0.02) are correlated to superficial wound infection (7%); obesity (p = 0.002) and COPD (p = 0.05) are correlated to aseptic dehiscence of the sternum (2%). The multivariate analysis identified low LVEF as the only independent risk factor for hospital mortality (p = 0.03), whereas obesity (p = 0.01) and peripheral vasculopathy (p = 0.03) proved to be correlated to postoperative mediastinitis; obesity (p < 0.001), year of the operation (p < 0.001), low LVEF (p = 0.007) and reoperation for bleeding (p = 0.01) were correlated to superficial infection of the wound and obesity turned out to be the only risk factor for aseptic dehiscence for the sternum (p = 0.003). The infection of the wound did not increase mortality, but it did increase the mean postoperative length of hospital stay (6 days for patients free of any complications of the wound versus 29.7 days for patients with complications of the wound). CONCLUSIONS: In patients with bilateral mammary grafts, obesity is the main risk factor for complications of the wound and this event greatly increases the length of the patient's hospital stay. Consequently, we suggest that bilateral mammary artery grafts be used carefully in this subset of patients.
Coronary Disease↗
Tesio catheters: findings in post-mortem examination.
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Arteriovenous Shunt, Surgical↗
Immunophenotype of acute lymphoblastic leukemia cells: the experience of the Italian Cooperative Group (Gimema).
The immunophenotype of 304 adult lymphoblastic leukemias (> 18 years) diagnosed on the basis of the FAB criteria was determined at the time of diagnosis using a panel of monoclonal antibodies. The series comprised cases diagnosed and immunophenotyped in 43 Italian centers (GIMEMA Cooperative Group) between April 1988 and June 1991. The immunophenotypic characterization consisted of two consecutive steps. The initial screening was based on the reactivity for TdT, HLA-Dr, CD7, CD10, CD13, CD19, CD24, CD33 and CD41. According to the results obtained, the second level of investigation assessed the positivity for intra cytoplasmic (Cy) Ig, CD1a, CD2, CD3, CD4, CD5, CD8 and CD20. Based on the hierarchical expression of the different B- and T-cell related antigens, each case was assigned to a given differentiation stage. B-lineage ALL were classified in five subgroups (B0-B4) and T-lineage ALL in four subgroups (T0-T3). Cases in which the blasts were lymphoid according to the FAB criteria, but expressed myeloid antigens in association with B- and T-lymphoid markers were defined as hybrid leukemias. As expected, CD10+ cases (B2-B3) were the most frequent within the B-lineage ALL (83.2% of cases). CyIg+ (B3) accounted for about 20% of CD10+ ALL. Twenty eight cases (13.4%) were at a pre-cALL stage (B0-B1) and of these, 8 (3.8% of the total series) were positive only for TdT and HLA-Dr (B0). Intermediate and mature thymic phenotypes (T2-T3) were predominant within the T-ALL (67.2%) groups. Five cases, were positive only for TdT and CD7 (CD5+), and classified as T0. 9.2% of cases fulfilled the definition of hybrid leukemia, largely in view of the co-expression of B-lymphoid and myeloid markers.(ABSTRACT TRUNCATED AT 250 WORDS)
Antigens, CD↗
Molecular and cellular analysis of human T lymphocytes expressing gamma delta T-cell receptor.
A minor subset of T lymphocytes expresses a CD3-associated TCR composed of gamma and delta chains. The majority of TCR gamma/delta+ cells lack surface CD4 and CD8 antigen and do not react with WT31 mAb. These negative criteria were utilized in early studies to identify TCR gamma/delta+ cells. More recently, mAb to TCR gamma/delta, selected in different laboratories, have permitted the direct identification of TCR gamma/delta+ cells and their subsets. TCR gamma/delta molecules were found to be heterogeneous in size and charge mobility. Two major forms of TCR gamma/delta could be identified that are characterized by the presence or absence of an inter-chain disulphide bond. Biochemical analysis originally suggested that a precise correlation existed between reactivity with BB3 or delta TCS1/A13 mAb and expression of a disulphide (C gamma 1-encoded) or non-disulphide linked (C gamma 2-encoded) form of TCR gamma/delta. However, more recent studies have indicated that these mAb react with the molecular product of V delta 2 or V delta 1, respectively, mAb directed to one or another form of TCR gamma/delta activate the functional program of the cell, leading to intracellular Ca++ mobilization, lymphokine production and triggering of the lytic machinery. Analysis of the target molecules for TCR gamma/delta-mediated recognition revealed that at least some TCR gamma/delta+ cells are capable of specific responses to (allo)antigen and that polymorphic determinants of class I molecules can be recognized (as shown by the specific lysis of P815 cells transfected with HLA-24 allele). Unlike TCR alpha/beta+ cells, TCR gamma/delta+ cells are homogeneously composed of cytolytic precursors, as shown by the analysis of a large panel of clones in both lectin-dependent and redirected killing assays. In spite of their LGL morphology, freshly isolated TCR gamma/delta+ cells do not lyse NK-sensitive targets but do so after exposure to rIL-2. A modest cytolytic activity, however, could be induced also in fresh cells by anti-TCR/CD3 mAb in a redirected killing assay. Analysis of the distribution of the subsets expressing different TCR gamma/delta types showed that BB3+ cells are prevalent in the peripheral blood and virtually absent in the thymus; in contrast, A13+ (delta TCS1+) cells represent the majority of TCR gamma/delta+ thymocytes. Electron microscopic analysis of fresh TCR gamma/delta+ cells showed an extended cytoplasm containing numerous electron-dense granules identifiable as primary lysosomes. Upon stimulation with IL-2, TCR gamma/delta+ cells, similar to other LAK cells, display an increase in their cytoplasmic granules together with a redistribution of cytoskeletal structures.(ABSTRACT TRUNCATED AT 400 WORDS)
Antibodies, Monoclonal↗