Biomedical subjects
Publications and source records attributed to M Ricci.
Pleural mesotheliomas are rare, and their diagnosis and treatment not clear. The case observed in our Department leads us to an analysis of the literature. This showed that differential diagnosis with pulmonary carcinoma is very difficult, even in cases of parietal mesothelioma; however local treatment may be performed even in malignant mesothelioma.
The effects exerted on the in vitro development of purified protein derivative (PPD)-specific or Dermatophagoides pteronyssinus group I (Der p I)-specific T cell lines (TCL) and T cell clones (TCC) by IL-4 or IFN-gamma addition or neutralization in human PBMC cultures were examined. PBMC from two normal individuals, which were stimulated with PPD and then cultured in IL-2 alone, developed into PPD-specific TCL and TCC able to produce IFN-gamma and IL-2 but not IL-4 and IL-5 (Th1-like). IFN-gamma or anti-IL-4 antibody addition in bulk cultures before cloning did not influence the PPD-specific TCL profile of cytokine production. In contrast, the addition of IL-4 resulted in the development of PPD-specific TCL and TCC able to produce not only IFN-gamma and IL-2 but also IL-4 and IL-5. PBMC from one atopic Der p I-sensitive patient, which were stimulated with Der p I and then cultured in IL-2 alone, developed into Der p I-specific TCL and TCC able to produce IL-5 and large amounts of IL-4 but no IFN-gamma (Th2-like). The addition in bulk cultures, before cloning, of either IFN-gamma or anti-IL-4 antibody markedly inhibited the development of Der p I-specific T cells into IL-4- and IL-5-producing TCL. Accordingly, the development into Der p I-specific Th2-like TCC was significantly reduced by the addition of IFN-gamma in bulk culture and was virtually suppressed by the presence of both IFN-gamma and anti-IL-4 antibody. These data suggest that the presence or the absence of IL-4 and IFN-gamma in bulk cultures of PBMC before cloning may have strong regulatory effects on the in vitro development of human CD4+ T cells into Th1 or Th2 clones.
The synthesis of a new series of N-2 alkylamino derivatives of 4,5-dihydro-s-triazolo[3,4-d]-1,5-benzothiazepine has been accomplished starting from 2,3-dihydro-1,5-benzothiazepin-4(5H)ones and their 2-methyl and 2-aryl derivatives. All the compounds were tested in vitro for their antimicrobial activity, but none of them showed remarkable activity. The tricyclic compounds 7a-j, 8a-j, 9a-j, 10a-j, and 11a-j were also screened for their CNS activity in mice and several of them showed interesting activity.
The cytokine secretion profiles of T cell lines (TCL) specific for purified protein derivative (PPD) or streptokinase (SK), contemporarily derived from nine atopic and nine nonatopic individuals, were compared. Upon stimulation with phorbol myristate acetate (PMA) plus anti-CD3 monoclonal antibody (mAb), all TCL from both atopics and nonatopics produced interleukin (IL)-2 and interferon (IFN)-gamma. The mean IL-2 production by PPD- or SK-specific TCL from both atopics and nonatopics was similar, whereas the mean IFN-gamma production by TCL derived from atopics was significantly lower. In addition, both PPD- and SK-specific TCL from atopics produced detectable amounts of IL-4 and IL-5, whereas the corresponding TCL derived from nonatopics did not. A total number of 107 and 99 PPD-specific CD4+ T cell clones (TCC) were then derived from TCL of 4 atopic and 4 nonatopic donors and assessed for their profile of cytokine production in response to stimulation with either PMA plus anti-CD3 mAb or the specific antigen. Under both these experimental conditions, virtually all PPD-specific TCC from both atopic and nonatopic individuals produced IL-2 and IFN-gamma. In contrast, the great majority of PPD-specific TCC derived from nonatopic individuals did not produce IL-4 and IL-5, whereas high proportions of PPD-specific TCC derived from atopic donors displayed the ability to produce noticeable amounts of IL-4 and IL-5 besides IL-2 and IFN-gamma. These data indicate that CD4+ T cells from atopic individuals are able to produce IL-4 and IL-5 in response to bacterial antigens, such as PPD and SK, that usually evoke responses with a restricted type-1 T helper (Th1)-like cytokine profile in nonatopic individuals. Aberrant IL-4 production by Th cells may represent one of the immune alterations responsible for enhanced IgE antibody production in atopic people.
We applied the technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO) split-dose method in order to evaluate the feasibility of assessing cerebral blood flow (CBF) changes with single photon emission tomography (SPET) during a motor activation task. Eleven normal subjects were studied using the Tomomatic 564 (Medimatic, DK). Five subjects were studied twice at rest and 6 subjects at rest and during a motor task performance (finger opposition movements). A total of 28 mCi of 99mTc-HMPAO was injected in 2 doses with a 1:3 ratio. The first scan was obtained after injection of 7 mCi at rest in all subjects. The second scan was obtained a few minutes later, after injection of the remaining dose (21 mCi), under similar resting conditions or during a motor task performance. The mean brain uptake was proportional to the amount of tracer injected and to the acquisition time for both the first scan (5263 +/- 1266 counts x mCi x min) and the second (5034.4 +/- 966 counts x mCi x min). The grey/white matter ratio was 1.67 +/- 0.019 and 1.67 +/- 0.097 for the two scans, respectively. A three-way analysis of variance (ANOVA) for repeated measure showed no significant effects of side, slice and region of interest (ROI) on the CBF in the 5 subjects studied twice at rest, and the mean regional CBF change was -0.2% +/- 5%.(ABSTRACT TRUNCATED AT 250 WORDS)
We analyzed 52 surgically excised ePTFE grafts used as secondary vascular access in chronic hemodialysis patients, structurally and histopathologically. Pseudoaneurysm formation at the site of repeated venipuncture was the main cause of surgical removal later than two years after implantation. Repeated needle punctures, twice per treatment, two or three times a week may result in a perigraft fibrous tissue capsule directly above areas where the graft was punctured. The delicate microporous structure of the graft wall was shown to be disrupted by needle punctures. The needle puncture sites were filled by surrounding connective tissue, and in one case, capillary formation was observed within the puncture sites. Examination by both light and scanning electron microscopy demonstrated identical patterns of pseudointima on the luminal surface. A thin pannus of endothelium-like cells, confined to the vicinity of the anastomoses, was noted in only four cases. On other areas of the luminal surface without endothelium, a red coagulum incorporating blood cells and fibrin was observed. Histological evidence of acute infection was absent in 61% of the cases and only 27% were considered to be clinically infected. Careful needle puncture technique, systematic rotation of puncture sites, and the use of rigorous aseptic technique are essential in preserving the long-term structural integrity of the vascular access, despite the good mechanical properties and reasonable good resistance to infection of ePTFE grafts.
We report the case of a 49 year old woman with clinical, electrophysiological and histochemical signs of facio-scapulohumeroperoneal dystrophy characterized by highly inflammatory changes. Lymphocyte typing by immunofluorescence and immunoperoxidase techniques on a muscle biopsy fragment revealed a large number of T8 cells at endomysial sites. There was no evidence of direct invasion of sound fibers by lymphocytes, which are thus unlikely to have exerted a primary cytotoxic action on the muscle tissue. Another finding was an increased number of macrophages in both endomysial and perivascular regions. Cell-mediated immunity did not play a significant role in the pathogenesis of our case, unlike other reported cases of polymyositis and facioscapulohumeral dystrophy with inflammatory findings.
Intestinal helminths from coecum and colon were studied in 93 equidae including 40 horses, 36 donkeys and 17 mules. A total of 38 species, 36 nematodes and 2 cestodes, were identified as follows: 1) Triodontophorus serratus, 2) Triodontophorus brevicauda, 3) Strongylus equinus, 4) Strongylus edentatus, 5) Strongylus vulgaris, 6) Cyathostomum tetracanthum, 7) Cyathostomum coronatum, 8) Cyathostomum labiatum, 9) Cyathostomum labratum, 10) Cyathostomum alveatum, 11) Cyathostomum pateratum, 12) Cyathostomum catinatum, 13) Cyathostomum sagittatum, 14) Cylicodontophorus bicoronatus, 15) Cylicocyclus radiatus, 16) Cylicocyclus auriculatus, 17) Cylicocyclus elongatus, 18) Cylicocyclus nassatus, 19) Cylicocyclus insigne, 20) Cylicocyclus leptostomus, 21) Cylicostephanus calicatus, 22) Cylicostephanus poculatus, 23) Cylicostephanus minutus, 24) Cylicostephanus longibursatus, 25) Cylicostephanus hybridus, 26) Cylicostephanus goldi, 27) Cylicostephanus ornatus, 28) Cylicostephanus skrjabini, 29) Poteriostomum ratzii, 30) Gyalocephalus capitatus, 31) Parascaris equorum*, 32) Probstmayria vivipara, 33) Draschia megastoma*, 34) Habronema muscae*, 35) Habronema majus*, 36) Setaria equina*, 37) Anoplocephala perfoliata, 38) Paranoplocephala mamillana. The asterisked species are those not usually localized in the examined material. The most frequent parasites were found in all three hosts. Species 1, 4, 6, 9, 10, 12, 21, 22, 30 and 35 showed significant differences in prevalence between horses and donkeys, the mule generally having intermediate values. Multiple infections and total worm burden appear to decrease in older animals (> 15 years). Parasite associations occur mostly at random as expected from the values of the respective total prevalences. Some significant excesses on expected values were recorded but not significant deficits. The total worm burden increases with the number of parasite species and the increase appears to follow an exponential pattern.
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Human bone marrow (BM) cells lacking T- and B-cell markers expressed RNA encoding interleukin (IL) 4 and secreted detectable amounts of IL-4 in supernatants in response to Fc epsilon or Fc gamma receptor (Fc epsilon R or Fc gamma R) cross-linking. In some experiments, IL-5 RNA expression in response to Fc epsilon R cross-linkage could also be detected. In contrast, RNA transcripts for, and secretion of, IL-2, IL-6, and interferon gamma were never observed. The presence of IL-3 in the cultures was essential for IL-4 production by non-B, non-T BM cells in response to Fc gamma R cross-linking and enhanced IL-4 RNA expression in response to Fc epsilon R cross-linking. Under the same experimental conditions, BM T and B lymphocytes, as well as peripheral blood T, B, and non-B, non-T cells, did not express IL-4 RNA. Prolonged incubation of non-B, non-T cells in IgE-free medium followed by extensive washing did not inhibit IL-4 production induced by anti-IgE antibodies, suggesting that the Fc epsilon R involved in the response has the characteristics of a high-affinity receptor. The Fc epsilon R+ cells were separated from the Fc epsilon R- cells by sorting non-B, non-T BM cell suspensions with fluorescein isothiocyanate-conjugated IgE and then assessed for both IL-4 RNA expression and alcian blue staining. Both IL-4-producing and alcian blue-positive cells segregated with the Fc epsilon R+ fraction. These data suggest that human BM cells, probably belonging to the mast cell and/or basophil lineage, are capable of producing IL-4 in response to Fc epsilon R or Fc gamma R cross-linkage.
A large number of CD4+ human T helper type 1 (Th1) clones specific for purified protein derivative and of Th2 clones specific for the excretory/secretory antigen of Toxocara canis, derived from the same individuals, were analyzed for both cytotoxic capacity and helper function for immunoglobulin (Ig) synthesis. The great majority of Th1, but only a minority of Th2 clones exhibited cytolytic activity. All Th2 (noncytolytic) clones induced IgM, IgG, IgA, and IgE synthesis by autologous B cells in the presence of the specific antigen, and the degree of response was proportional to the number of Th2 cells added to B cells. Under the same experimental conditions, Th1 (cytolytic) clones provided helper function for IgM, IgG, and IgA, but not IgE, synthesis with a peak response at 1:1 T/B cell ratio. At higher T/B cell ratios, a strong decrease of Ig synthesis was observed. All Th1 clones lysed Epstein-Barr virus transformed autologous B cells pulsed with the specific antigen. The decrease of Ig production at high T/B cell ratios correlated with the lytic activity of Th1 clones against autologous antigen-presenting B cell targets. These data suggest that Th1 differ from Th2 human T cell clones not only for their profile of cytokine secretion, but also for cytolytic potential and mode of help for B cell Ig synthesis.
We have established a large panel of T-cell clones (TCCs) specific for Dermatophagoides pteronyssinus and Lolium perenne group I grass pollen allergens (total, 61) and for tetanus toxoid and protein purified derivative bacterial antigens (total, 38) from the peripheral blood of two atopic individuals and then analyzed their ability to produce interleukin 4 (IL-4), IL-5, and interferon gamma (IFN-gamma). Upon stimulation with phorbol 12-myristate 13-acetate plus anti-CD3 antibody, the great majority of TCCs specific for bacterial components was able to produce both IL-4 and IFN-gamma, whereas most D. pteronyssinus- and L. perenne group I-specific TCCs produced IL-4, but no, or limited, IFN-gamma. Moreover, the mean amounts of IL-4 and IFN-gamma released by allergen-specific TCCs were significantly higher and lower, respectively, than the mean amounts produced by TCCs specific for bacterial components. Under the same experimental conditions, virtually all allergen-specific TCCs, but only one-third of tested TCCs specific for bacterial components, expressed IL-5 RNA and secreted IL-5 in their supernatants. Eighteen TCCs (nine specific for allergens and nine specific for bacterial components) were also assessed for their ability to induce IgE synthesis by autologous B cells in response to stimulation with the specific antigen. Under these experimental conditions, all allergen-specific TCCs, but only one-third of TCCs specific for bacterial components that produced IL-4 but no, or little, IFN-gamma induced the synthesis of detectable amounts of IgE. The demonstration that most allergen-specific helper T cells in atopic individuals are able to produce high amounts of IL-4 (and IL-5), but no IFN-gamma, may explain why allergens induce production of IgE antibodies and increase eosinophils.
A total number of 132 T cell clones (TCC) were obtained by PHA-stimulation of single T cells from mononuclear cell suspensions of conjunctival flogistic infiltrates of three patients with vernal conjunctivitis (VC). The phenotype and functional properties of these TCC were compared with those of 122 TCC contemporarily established from PB mononuclear cell suspensions of the same patients, 120 TCC established from lymph nodes of three patients with nonspecific hyperplastic lymphoadenitis and 159 TCC established from thyroid lymphocyte infiltrates of three patients with Graves' disease. The great majority of conjunctival TCC displayed the CD4+ CD8- phenotype (CD4/CD8 ratios ranging from 6.1 to 7.0), whereas the mean CD4/CD8 ratios for control TCC ranged from 0.9 to 2.4. After stimulation with either PHA or PMA plus anti-CD3 mAb, conjunctival TCC differed from control TCC for their ability to produce cytokines. In particular, a large number of conjunctival TCC produced IL-4, but no, or limited amounts of, IFN-gamma, whereas no difference was observed between conjunctival and control TCC with regard to the production of IL-2. The failure of IFN-gamma production by conjunctival TCC was apparently not caused by delay or block in cytokine production, but actually reflected the lack of IFN-gamma transcription. Virtually all conjunctival TCC able to produce IL-4, but not IFN-gamma, as well as most of those producing both cytokines, provided helper function for IgE synthesis in allogeneic normal B cells. The accumulation in the conjunctiva of patients with vernal conjunctivitis of CD4+ T cells that, apart from the production of IL-2, resembles murine Th2 cells for their profile of cytokine production and helper function suggests a possible role for these cells in the pathogenesis of the disease.
The availability of high efficiency T-cell cloning techniques recently allowed the identification and characterization of clones derived from the thyroid infiltrate of patients with autoimmune thyroid diseases. Phenotypical and functional analysis of T-cell clones obtained from thyroid infiltrates of patients with Hashimoto's thyroiditis show that most of them are progenies of CD8+ cytolytic T cells with natural killer activity. This phenomenon, of potential importance in tissue damage, is markedly less pronounced in Basedow's disease glands. In both Hashimoto's thyroiditis and Basedow's disease only a minority of clones appear to be specific for autologous thyroid cells and most of them are potent interferon-gamma producers, while increased secretion of tumor necrosis factor-alpha is observed only in Hashimoto's thyroiditis. In contrast with normal lymphoid tissue, only very few T cell clones derived from both BD and HT infiltrates were able to produce detectable amounts of IL-4, suggesting that most of the thyroid-infiltrating T cells represent quite homogeneous populations of Th1-type "inflammatory" T cells. This peculiar potential of lymphokine secretion could play a role in the expression and/or maintenance of thyroid autoimmunity and thyroid functional damage.
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One-hundred and seventy-four consecutive patients who underwent curative resection for gastric and colorectal cancer between 1983 and 1985 were studied prospectively to evaluate the roles of sequential carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA) and Ca 19-9 determinations and independent clinical examinations, in the early diagnosis of resectable recurrences. Sixty-six recurrences (33 from gastric and 33 from colorectal cancer) were detected between 6 and 42 months after primary surgery. In gastric cancer CEA, TPA and Ca 19-9 showed a sensitivity of 64%, 73% and 60% respectively and a specificity of 67%, 65% and 54% respectively. Nine patients (27%) underwent surgical treatment for recurrent disease, and four of these (44.4%) had resectable recurrence, for a total resectability rate of 12%. Of these four patients, three are still living after 12, 36 and 44 months respectively from re-operation without evidence of neoplastic disease. In one of these patients, re-operation was performed on the basis of the elevation of the three markers, without any other clinical sign of disease. This patient had a resectable solitary hepatic recurrence. In colorectal cancer. CEA, TPA and Ca 19-9 showed a sensitivity of 73%, 73% and 49% respectively, and a specificity of 77%, 87% and 97% respectively. Fourteen patients (42.4%) underwent surgical treatment for recurrent disease and eight of these (57%) showed resectable recurrence, for a total resectability rate of 24.2%. Six patients are still living after 9, 16, 21, 31, 41 and 53 months respectively from re-operation without evidence of neoplastic disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Phytohemagglutinin (PHA)-induced human T cell clones (TCC) derived from conjunctival flogistic tissues of 3 patients with vernal conjunctivitis produced unusually high amounts of interleukin-4 (IL-4) and no, or limited amounts of, gamma-interferon (IFN-gamma). Allergen (Dermatophagoides pteronyssinus or Lolium perenne group I)-specific TCC derived from peripheral blood of two atopic donors produced significantly higher amounts of IL-4 and significantly lower amounts of IFN-gamma than TCC specific for bacterial antigens (tetanus toxoid and PPD) contemporarily established from the same donors. These data provide evidence for a compartimentalization of Th2-like helper T cells in target organs and in the allergen-specific T cell repertoire of allergic patients. Non-B, non-T bone marrow cells could produce IL-4, but not IL-2 or IFN-gamma, in response to cross-linkage of Fc epsilon type I receptors. These cells may further contribute to the maintenance and amplification of allergic inflammation.
A large series of T cell clones (TCC) specific for purified protein derivative (PPD) of Mycobacterium tuberculosis (total 60) or Toxocara canis excretory/secretory (TES) antigen (total 69) were established from the peripheral blood of two healthy individuals and analyzed for their profile of cytokine production in response to stimulation with either the specific antigen or the polyclonal activator phorbol myristate acetate plus anti-CD3 antibody. Under both these experimental conditions, the great majority of PPD-specific TCC secreted IL-2 and IFN-gamma but not, or limited amounts of, IL-4 and IL-5. In contrast, most TES-specific TCC secreted IL-4 and IL-5 but not, or limited amounts of, IL-2 and IFN-gamma. PPD-specific TCC that failed to secrete IL-4 and IL-5, and TES-specific TCC that failed to secrete IL-2 and IFN-gamma, were found to lack transcripts for IL-4 and IL-5, or for IL-2 and IFN-gamma, respectively. During the course of the study, over a 6-mo period, the functional phenotype of both TES- and PPD-specific TCC was repeatedly assessed and remained constant. These data demonstrate that T cells with stable Th1 or Th2 functional pattern exist not only in mice but also in humans and suggest that in the course of natural immunization certain infectious agents preferentially expand T cell subsets with stable and definite profile of cytokine production.