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Biomedical subjects

A Corradi

Publications and source records attributed to A Corradi.

At least 37 records · Page 2Linked to original sources

Zinc, thymic endocrine activity and mitogen responsiveness (PHA) in piglets exposed to maternal aflatoxicosis B1 and G1.

Growth retardation, thymic involution and impaired peripheral immune efficiency are constant events in piglets exposed to maternal aflatoxicosis. Zinc may play a key role because of its requirement for good immune responses, including thymic endocrine activity. Zinc is required to activate a thymic hormone, i.e. thymulin (ZnFTS), which is responsible for cell-mediated immunity. Zinc deficiency and decreased thymic endocrine activity are present in piglets fed from sows exposed to aflatoxins (AF) B1 and G1 as compared with healthy control piglets. In particular, active ZnFTS is decreased while concentrations of inactive thymulin (FTS) are high. The in vitro addition of zinc up to the plasma samples induces a reduction of inactive thymulin. The lymphocytes mitogen responsiveness (PHA) is decreased and a thymic cortical lymphocyte depletion is also present. These data suggest that the thymic defect, followed by impaired peripheral immune efficiency, may largely depend by the low peripheral zinc bioavailability to saturate all thymulin molecules produced.

Aflatoxin B1↗

Experimental infection of pigs with a thymidine kinase negative strain of pseudorabies virus.

Sixteen 20 day old pigs, devoid of neutralizing antibody to pseudorabies virus (PRV), were divided into two groups of eight, an the animals of each group were housed in a separate unit. In each group 6 pigs were inoculated intranasally with the thymidine kinase (TK-) mutant (Group 1) or the field strain of PRV (Group 2), each pig receiving an inoculum of 4 ml. The remaining 2 pigs in each group served as uninoculated controls. The only clinical sign observed in the pigs of Group 1 was a transient febrile reaction, in the case of six pigs inoculated with the TK- mutant of PRV, whereas no signs of disease were seen in the uninoculated controls. The virus was isolated from the 6 infected pigs of the group only on post infection day (PID) 2, whereas it was never isolated from the controls. By contrast, the pigs of Group 2, had a severe clinical response and one, among those that were inoculated with the field strain of the PRV, died on PID 9. Virus was consistently isolated from all pigs of Group 2, inoculated and control. On PID 30 all pigs, i.e. the 8 of Group 1 and 7 of the Group 2 which survived to the infection, were subjected to dexamethasone (DMS) treatment. After DMS treatment virus was never isolated from the nasal swabbings obtained from the pigs of Group 1, whereas it was consistently isolated from pigs of Group 2. After 30 d from the start of DMS treatment the pigs were killed and several tissues were collected from each pig for virus detection, by isolation in tissue culture and by PCR analysis. At necropsy no lesions were found in pigs of Group 1, whereas acute pneumonia and gliosis in the trigeminal ganglia were observed in pigs of Group 2. Virus was never isolated from any of the tissues taken from pigs of both, Group 1 and Group 2, nevertheless sequences of PRV were detected by PCR analysis in the trigeminal ganglia of the pigs of both Groups.

Animals↗

Mab21, the mouse homolog of a C. elegans cell-fate specification gene, participates in cerebellar, midbrain and eye development.

A multitude of regulatory genes are involved in phylogenetically conserved developmental cascades required for the patterning, cell-type specification, and differentiation of specific central nervous system (CNS) structures. Here, we describe the distribution of a mouse transcript encoding a homolog of the C. elegans mab-21 gene. In the nematode tail, mab-21 is required for the short-range patterning and cell-fate determination events mediated by egl-5 and mab-18, two homeobox genes homologous to Abd-B and Pax6, respectively. In mouse midgestation embryogenesis, Mab21 is expressed at its highest levels in the rhombencephalon, cerebellum, midbrain, and prospective neural retina. Our data and the genetic interactions previously documented in the nematode suggest that Mab21 may represent a novel, important regulator of mammalian cerebellum and eye development.

Animals↗

Expression of human CD44v6 in non-small-cell lung cancer.

INTRODUCTION: The CD44 is a membrane glycoprotein that functions as lymph node homing receptor in lymphocyte activation and is involved in homo- and heterotypic cell adhesion. In several tumor cell lines the expression of splice variants (CD44v6 and CD44v7) are correlated with the metastatic potential and confer an advantage in the early steps of the metastatic cascade. In our study we examined 35 cases of non-small-cell lung cancers (NSCLC) in order to detect the presence of CD44v6 and to compare its expression with the histologic type, degree of differentiation, stage of the tumor and survival of the patients. METHODS: CD44v6 expression in frozen tissue sections of 35 patients with NSCLC who underwent pneumonectomy or lobectomy was analyzed with the VFF-7 monoclonal antibody that detected the CD44v6 variant. The data on survival were analyzed by the actuarial method and compared by the log rank test. RESULTS: The expression of CD44v6 occurred in all the 20 cases of epidermoid carcinomas tested and in 2 out of the 3 cases of undifferentiated large cell carcinoma and was absent in all the 12 adenocarcinomas. No relationship was found between the presence of this marker and the grading or the stage of the pathology. The 3-year survival rate was 73% for CD44v6-positive and 65% for CD44v6-negative cancer and the comparison was not statistically significant. CONCLUSION: These results suggest that in lung cancer the expression of CD44v6 is not a useful prognostic factor.

Adenocarcinoma↗

Clinical utility of prothrombin fragment 1+2, thrombin antithrombin III complexes and D-dimer measurements in the diagnosis of deep vein thrombosis following total hip replacement.

BACKGROUND: Measurements of prothrombin fragment 1+2 (F1+2), thrombin antithrombin III complexes (TAT) and D-dimer plasma levels have been proposed as non-invasive screening tests to exclude postoperative deep venous thrombosis (DVT). We investigated the diagnostic efficacy of these coagulation activation markers to rule out postoperative DVT in patients undergoing hip surgery under antithrombotic prophylaxis. METHODS: In this substudy of a randomized double-blind thrombosis prophylaxis trial comparing three doses of desirudin (10, 15 or 20 mg b.i.d.) with unfractionated heparin (5000 IU t.i.d.) we used ELISA procedures to measure F1+2, TAT and D-dimer in 159 patients undergoing total hip replacement at baseline (day 0) and on postoperative days 1, 3 and 6. Bilateral venography was performed in all cases 8-11 days after surgery. RESULTS: For the F1+2 assay sensitivity ranged from 73 to 83% in the three postoperative days investigated, and negative predictive value (NPV) from 68 to 74%. For TAT and D-dimer sensitivity ranged from 71 to 73% and from 71 to 83% and NPV from 61 to 65% and from 61 to 74% respectively. INTERPRETATION: In terms of sensitivity and NPV F1+2 and D-dimer are equivalent and are superior to TAT. However, their accuracy is too low to rule out the presence of DVT after hip surgery under antithrombotic prophylaxis.

Anticoagulants↗

Activation-related differences in HLA class I-bound peptides: presentation of an IL-1 receptor antagonist-derived peptide by activated, but not resting, CD4+ T lymphocytes.

We have compared by reverse phase HPLC the set of peptides eluted from HLA class I molecules in resting and activated CD4+ Jurkat cells. Two peptides were identified that are presented de novo upon activation. After sequencing, one of these peptides turned out to derive from IL-1R antagonist (IL-1Ra). In keeping with this observation, we found that activated, but not resting, Jurkat cells express IL-1Ra. These data indicate that activation of a CD4+ T cell line may result in presentation of peptides derived from proteins expressed de novo after activation. Since IL-1Ra was not known to be expressed by cells of the T lineage, we also investigated its pattern of expression in normal T lymphocytes. Reverse transcriptase-PCR analyses allowed us to demonstrate that IL-1Ra is expressed upon activation by normal CD4+ lymphocytes from peripheral blood and by thymocytes, but not by CD8+ T cells. Interestingly, of the two forms of IL-1Ra that have been detected in different cell lineages, the intracellular one and the secreted one, only the former is expressed by activated CD4+ T cells.

Antigen Presentation↗

Mmot1, a new helix-loop-helix transcription factor gene displaying a sharp expression boundary in the embryonic mouse brain.

Several genetic factors have been proven to contribute to the specification of the metencephalic-mesencephalic territory, a process that sets the developmental foundation for prospective morphogenesis of the cerebellum and mesencephalon. However, evidence stemming from genetic and developmental studies performed in man and various model organisms suggests the contribution of many additional factors in determining the fine subdivision and differentiation of these central nervous system regions. In man, the cerebellar ataxias/aplasias represent a large and heterogeneous family of genetic disorders. Here, we describe the identification by differential screening and the characterization of Mmot1, a new gene encoding a DNA-binding protein strikingly similar to the helix-loop-helix factor Ebf/Olf1. Throughout midgestation embryogenesis, Mmot1 is expressed at high levels in the metencephalon, mesencephalon, and sensory neurons of the nasal cavity. In vitro DNA binding data suggest some functional equivalence of Mmot1 and Ebf/Olf1, possibly accounting for the reported lack of olfactory or neural defects in Ebf-/- knockout mutants. The isolation of Mmot1 and of an additional homolog in the mouse genome defines a novel, phylogenetically conserved mammalian family of transcription factor genes of potential relevance in studies of neural development and its aberrations.

Amino Acid Sequence↗

Modulation of host cell activation during feline immunodeficiency virus (FIV) infection.

The authors describe the mitogenic effect of feline immunodeficiency virus (FIV) infection (1) in vitro, on feline resting peripheral blood lymphocytes (PBL), and (2) in vivo, in experimentally infected cats. Infected PBL were more readily recruited than non-infected PBL, into the G1 phase of the cell cycle and showed increased expression of the specific cell-cycle markers p53 and p56. In-vivo lymphocyte activation following FIV infection was demonstrated by increased germinal centre activity in infected lymph nodes, together with a high expression of CD30, a B-cell activation marker. These results suggest that early events in FIV infection include modulation of host cell activation. Possible implications for pathogenesis are discussed.

Animals↗

FIV induced encephalopathy: early brain lesions in the absence of viral replication in monocyte/macrophages. A pathogenetic model.

FIV induced encephalopathy represents a model for the study of the neuropathogenesis of AIDS. It has yet to be determined whether massive viral replication is a prerequisite for the development of early brain lesions. Using a drug delivery system developed by us, we have shown that early encephalic lesions appear in FIV infected subjects even when viral transport within the brain has been markedly reduced or blocked.

Acute Disease↗

Coagulation activation markers in the prediction of venous thrombosis after elective hip surgery.

BACKGROUND: Despite prophylaxis, deep vein thrombosis (DVT) after hip surgery continues to occur frequently. Thus it would be helpful if before surgery patients at higher risk of DVT could be identified and more adequate prophylaxis given. As part of an international study on the prevention of DVT after total hip replacement, we investigated whether preoperative levels of three coagulation activation markers, prothrombin fragment F1 + 2 (F1 + 2), thrombin-antithrombin III complexes (TAT) and D-dimer, correlate with results of postoperative venography. METHODS: 159 patients undergoing total hip replacement were randomized to receive 10, 15 or 20 mg desirudin bid or 5000 IU unfractionated heparin tid immediately before surgery and then for 11 days, until bilateral venography was performed. Preoperative F1 + 2, TAT and D-dimer plasma levels were measured using ELISA procedures. As no difference among anticoagulant treatments or in the interaction between treatments and DVT was detected for any of the three variables, results are reported as pooled data. FINDINGS: The frequency of DVT was 18.8% in the low (0.75-1.33 nM) vs 65.7% in the high third of distribution (1.77-3.47 nM) of F1 + 2 (p < .001), 27.3% in the low (2.00-2.50 micrograms/l) vs 57% in the high third (5.10-61.00 micrograms/l) of TAT (p = .042), and 29.4% in the low (39-59 micrograms/l) vs 57.1% in the high third (129-651 micrograms/l) of D-dimer (p = .051). INTERPRETATION: Preoperative F1 + 2, TAT and D-dimer levels are associated with the risk of development of DVT after total hip replacement.

Adult↗

[Experimental tracheal transplantation. Literature review and proposal of an original surgical technique].

The reconstruction of the trachea after wide resections remains a critical surgical problem. Our aim has been to replace trachea with a tissue easy to be vascularized, that permits a simple reconstruction, not requiring an immunosuppressive regimen. We have used a segment of cryopreserved aorta. In the first phase the thoracic aorta of 10 rabbits was excised obtaining 20 segments that were cryopreserved. Ten segments were implanted in the omentum of 10 rabbits that were sacrificed on postoperative day 7, 14 and 21. The histologic examination of the grafts showed the presence of neovascularization after 7 days with obliteration of the lumen by fibroblasts after 14 days. In the next phase the cryopreserved aorta replace an excised segment of trachea. The survived animals were sacrificed 7 and 14 days after the operation. The histologic examination showed the neovascularization of the graft and the absence of rejection.

Animals↗

cDNA sequence, map, and expression of the murine homolog of GTBP, a DNA mismatch repair gene.

DNA mismatch repair genes (MMR) have been actively studied in humans for their role in cancer susceptibility. Recently, GTBP, a new member of the MMR gene family, has been cloned and found to encode a 160-kDa protein that forms a heterodimer with hMSH2. Our group has isolated and characterized the mouse homolog of GTBP. The transcript, termed Gtmbp (G/T mismatch-binding protein), encodes a protein highly similar to its human counterpart. The gene is markedly conserved across species and maps to the distal portion of mouse chromosome 17, in a region homologous to human 2p. One Gtmbp-related sequence maps to proximal mouse chromosome 4. Studies of the expression of Gtmbp suggest that its regulated transcription is tightly linked to the level of DNA replication, consistent with the protein's DNA proofreading function.

Animals↗

Markers of hemostatic system activation during thromboprophylaxis with recombinant hirudin in total hip replacement.

Coagulation activation markers were studied in 148 patients undergoing total hip replacement under recombinant-hirudin (Desirudin, Revasc) prophylaxis with the aim of investigating the efficacy and safety of this anticoagulant compared with heparin in terms of biological effects on coagulation variables and bleeding. Hirudin (10, 15 or 20 mg s.c. b.i.d.) or unfractionated heparin (5000 IU s.c. t.i.d.) was administered immediately before surgery and continued for 8-12 days. Activated partial thromboplastin time (aPTT), prothrombin activation fragment F1 + 2 (F1 + 2), thrombin-antithrombin III complexes (TAT) and D-dimer were measured at baseline and on postoperative days 1,3 and 6, immediately before the morning injection. In comparison with baseline values, heparin had little effect on aPTT whereas the three hirudin doses prolonged aPTT significantly with no differences among the three doses. Moreover, there were no group differences in perioperative or cumulative blood loss or transfusion requirements. F1 + 2 fragment, TAT and D-dimer plasma levels were higher than at baseline during the entire postoperative period, with different trends (F1 + 2 increasing, TAT decreasing, D-dimer increasing, decreasing and then increasing again), but without significant differences among the four treatment groups. Our findings suggest that specific inhibition of thrombin seems a safe and efficacious mode of blocking thrombin activity after hip surgery although it does not prevent thrombin generation.

Adult↗

Synthesis and secretion of interleukin-1 alpha and interleukin-1 receptor antagonist during differentiation of cultured keratinocytes.

Keratinocytes produce interleukin-1 alpha (IL-1 alpha) and the epithelial variant of its inhibitor, interleukin-1 receptor antagonist (icIL-1ra). Both IL-1 alpha and icIL-1ra lack a secretory signal peptide; however, some icIL-1ra is found in the supernatants of cultured keratinocytes. The lack of correlation with the release of the cytosolic enzyme lactate dehydrogenase suggests that icIL-1ra can be actively secreted. Brefeldin A fails to block icIL-1ra release, suggesting that this protein may be externalized by keratinocytes through a leaderless pathway of secretion. Only minute amounts of soluble extracellular IL-1 alpha are detected: however, both IL-1 alpha and icIL-1ra can be released from the external face of the keratinocyte plasma membrane by mild acidic treatment, suggesting that IL-1 alpha can also be secreted by keratinocytes. The observation of membrane-associated IL-1 alpha and icIL-1ra might reflect an autocrine loop of regulation. Support for this hypothesis comes from the finding that keratinocytes, when exposed to exogenous recombinant IL-1 alpha, increase their content in both IL-1 alpha and IL-1ra mRNA. When keratinocytes are subjected to counterflow centrifugal elutriation, three major cell populations are obtained, representing three different degrees of keratinocyte differentiation. Cells from all populations synthesize IL-1 alpha and IL-1ra: however, while IL-1 alpha is uniformly distributed in cells from all maturational stages, IL-1ra accumulates in large, more differentiated keratinocytes. Changes in the ratio of IL-1ra to IL-1 alpha production and secretion by keratinocytes at different degrees of maturation might contribute to the control of growth and differentiation of human skin.

Cell Differentiation↗

A study of two mutant strains of pseudorabies virus (PRV) unable to express thymidine kinase (TK) function.

Two mutant strains of pseudorabies virus (PRV) were selected from the virulent 86/27V virus treated with chemical drugs. The viruses, named 6A1 and 6C2, respectively, appeared to be unable to express thymidine kinase function, as demonstrated by the autoradiography test. They showed a reduced virulence for some susceptible animal species (chickens, mice, rabbits, calves, lambs and piglets) and virus was isolated sporadically. The mutant viruses appeared to be able to protect animals against infection with the virulent strain of PRV. At gross, as well as at histological examination, no lesions in apparatus, system and tissues were detected in pigs inoculated with 6A1 and 6C2 viruses. By contrast, rabbits treated with 6C2 mutant strain presented lymphomononucleated cuffs, microgliosis, and neuronophagia in some areas of the brain. This focal spreading, together with the absence of neuronal necrosis and intranuclear inclusions, suggest an infection induced by a modified strain of PRV.

Animals↗