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Biomedical subjects

R Gerli

Publications and source records attributed to R Gerli.

At least 91 records · Page 5Linked to original sources
PubMed1990

A fibrillar elastic apparatus around human lymph capillaries.

A fibrillar elastic apparatus around the wall of human lymph capillaries is demonstrated by means of histochemical and ultrastructural techniques. This apparatus consists of three interlinked components listed here in order of increasing distance from the capillary wall: 1) oxytalan fibres connected to the abluminal surface of the endothelial cells, known also as "anchoring filaments" and consisting of bundles of microfibrils; 2) elaunin fibres consisting of microfibrils and a small amount of elastin; and 3) typical elastic fibres consisting of microfibrils and abundant elastin. The microfibrillar constituent has similar ultrastructural features in the three components of the elastic apparatus. Microfibrils have a diameter of 12-14 nm, an electron-transparent core and a wall with 3-5 electron-dense subunits and oblique cross striations with a period of 15-17 nm. Microfibrils are the common element of the three components of the elastic apparatus and they link them to one another and to the elastic network of the perivascular connective tissue. An elastic apparatus was not found around blood capillaries and it can thus provide a histological marker to identify lymph capillaries. The possible role of the lymphatic elastic apparatus in the physiological activity of the lymphatic absorbing network is discussed and it is proposed that its disconnection from the elastic network of the tissue may promote pathological conditions such as lymphoedema or diseases related to impaired immune responses.

Actin Cytoskeleton↗
PubMed1990

Activation of cord T lymphocytes. II. Cellular and molecular analysis of the defective response induced by anti-CD3 monoclonal antibody.

Despite the fact that the percentage of circulating CD3-positive cells is similar in cord and adult blood, the proliferative response induced by anti-CD3 monoclonal antibody (mAb) was impaired in the majority of human cord peripheral blood mononuclear cell (PBMC) samples we tested. The cell proliferative defect was associated with low interleukin 2 (IL 2) gene expression and scant IL 2 production. However, interleukin 2 receptor was fully expressed at both the mRNA and protein levels. Such a finding is consistent with the observation that exogenous recombinant IL 2 is able to boost the anti-CD3-mediated response of cord PBMC. Furthermore, when anti-CD3 and phorbol myristate acetate (PMA) were added together, they exerted a very marked synergistic effect on both the proliferation of, and IL 2 production by, cord PBMC. The addition of allogeneic antigen presenting cells plus soluble anti-CD3 or Sepharose-coupled anti-CD3 mAb to the cord T cell cultures had no significant effect on proliferation, whereas both elicited good mitogenesis of adult T cells. Moreover, addition of exogenous recombinant interleukin 1 to anti-CD3-stimulated T cells failed to trigger any proliferation in either adult or cord samples. Since the combination of PMA and calcium ionophore A23187 is effective in triggering optimal proliferation of cord T cells, the defect would seem to be associated with a failure in transmembrane transduction of the activation signals provided by the anti-CD3 stimulus for the cord T cell.

Antigen-Presenting Cells↗
PubMed1990

Selection of a panel of monoclonal antibodies for monitoring residual disease in peripheral blood and bone marrow of interferon-treated hairy cell leukaemia patients.

A panel of monoclonal antibodies (mAbs) directed against B-cell and hairy cell leukaemia (HCL)-associated antigens was used to identify residual hairy cells in the peripheral blood and/or bone marrow samples from 20 patients with HCL, following treatment with interferon-alpha (IFN-alpha) or interferon-beta (IFN-beta). In all cases, hairy cells retained their characteristic phenotype, e.g. positivity for CD22, CD11c, CD25, CD32, and the HCL-associated trimeric protein (t-GP) recognized by the mAbs HML-1, B-ly7, LF61 and Ber-Act8. The most specific marker for identifying a small percentage of hairy cells in peripheral blood cytospins, was t-GP. In alkaline phosphatase/anti alkaline phosphatase (APAAP) stained preparations, t-GP+ hairy cells (provided with large cytoplasm and hairy surface) could be usually distinguished from t-GP+ normal lymphocytes (small-sized cells with smooth surface). In doubtful cases the percentage of residual hairy cells could exactly be estimated by double immunofluorescence staining for CD22 (B-cell marker) and t-GP. The rationale of the test is based on the finding that the small percentage (about 1%) of t-GP+ lymphocytes circulating in the peripheral blood of normal individuals are T-cells of the CD8 subset and not B-cells. The best markers for identifying residual hairy cells in routine bone marrow biopsies were CD45RA (mAb 4KB5) and CD20 (mAb L26). Immunohistological labelling was superior to morphological examination in picking up scattered hairy cells in bone marrow biopsies showing either severe hypoplasia or exuberant hyperplasia of normal haemopoietic series.

Antibodies, Monoclonal↗
PubMed1990

Basis for defective proliferation of peripheral blood T cells to anti-CD2 antibodies in primary Sjögren's syndrome.

Anti-CD2-induced T cell proliferation was analyzed in the peripheral blood samples of 31 primary and 8 secondary untreated Sjögren's syndrome patients. Anti-CD2-stimulated PBMC proliferation was very low in about one-third of primary Sjögren's syndrome samples, despite the number of CD2+ cells being similar in primary and secondary Sjögren's syndrome and normal PBMC samples. The depressed response to anti-CD2 was mainly found in anti-Ro+/La+ patients. Experiments on purified T cells demonstrated that a defect at the T cell level was responsible for the anti-CD2 unresponsiveness. Cell proliferation failure was associated with poor IL-2 and IL-2 receptor mRNA expression and, consequently, IL-2 and IL-2 receptor synthesis. Since defective anti-CD2-induced mitogenesis could be reversed by phorbol myristate acetate, but not calcium ionophore A23187, it is probably correlated with impaired protein kinase C activation. Comparison of anti-CD2-triggered PBMC proliferation in treated and untreated patients and a long-term study of nine patients showed that the defect is a stable characteristic in primary Sjögren's syndrome patients, but that it can be reversed by pharmacological immunosuppression.

Adrenal Cortex Hormones↗
PubMed1989

Activation of cord T lymphocytes. I. Evidence for a defective T cell mitogenesis induced through the CD2 molecule.

A study was carried out on cord blood T cell activation via the CD2-mediated pathway. Despite similar percentages of circulating CD3+ and CD2+ cells in adult and cord blood, the proliferation of cord PBMC to the anti-CD3 mAb and cord T cells to anti-CD2 mAb were defective. The T cell CD3-surface structure was normally able to control CD2-mediated activation, as its modulation by a non-mitogenic anti-CD3 mAb blocked cord PBMC proliferation induced by anti-CD2 mAb. CD2-stimulated cord T cells did not proliferate and did not produce a significant amount of IL-2 in culture, although they expressed the IL-2R. This observation was confirmed by the optimal proliferation of CD2-induced cord T cells when rIL-2 was added. Despite the alternative T cell activation pathway is monocyte-independent in adults, the defective cord T cell activation via the CD2 molecule could also be bypassed by the addition of PMA, small amounts of either autologous or allogeneic adult and cord AC or simply rIL-1 alone. Our findings provide evidence for an intrinsic functional defect in cord CD2-mediated T cell activation, which is linked to an impaired increase of free cytoplasmic calcium, as confirmed by the effectiveness of calcium ionophore A23187 in restoring a good CD2-induced cord T cell proliferation and by measurement of cellular calcium uptake after activation via the CD2 molecule. The characteristics of cord T cells revealed by this study recall the thymocyte functional pattern and may represent functional expression of the previously described phenotypic immaturity of cord T cells.

Antibodies, Monoclonal↗
PubMed1989

X-ring Turner's syndrome with combined immunodeficiency and selective gonadotropin defect.

A rare association of chromosomal, immunological and endocrine defects is described in a young woman with short stature, recurrent pulmonary infections and primary amenorrhea. Cytogenetic studies showed a 45, X karyotype in 65% of peripheral blood lymphocytes and 46,Xr(X) (p22q27) karyotype in the remaining 35%. Severe immunodeficiency was revealed by phenotypical and functional studies and a selective gonadotropin defect was disclosed by endocrinological investigations. An attempt is made to explain the coexistence of the three abnormal pictures.

Adult↗
PubMed1989

Defective natural killer cell activity in puerperal hyperprolactinemia.

Prolactin (PRL) influences immune reactivity in animals and in humans and both T-cell abnormalities and reduced natural killer (NK) cell activity have been reported in women with pathological hyperprolactinemia. To investigate further the possible interactions between PRL and the immune system in humans, we analysed T-cell phenotypes and NK cell activity in 15 women with physiological hyperprolactinemia of the puerperium and in 45 age-matched healthy normal cycling women. Puerperal women displayed a normal T-cell phenotype but a significant reduction in the number of Leu-7+ and Leu-11+ cells, associated with a decreased NK cell activity, as measured against K-562 target cells. There was a significant inverse correlation between the raised serum PRL levels and both the number of Leu-7+ cells and NK cell activity. These data confirm an important immunoregulatory role for PRL in humans and suggest a direct inhibitory effect of the chronically raised PRL concentrations on the maturation of NK cells.

Female↗
PubMed1989

T-cell response to anti-CD2 monoclonal antibodies in Down's syndrome.

Peripheral blood mononuclear cells from 10 subjects with cytogenetically documented Down's syndrome (DS) and from 10 age- and sex-matched healthy controls were assayed for their ability to proliferate in response to phytohaemagglutinin, anti-CD3 (OKT3), or anti-CD2 (T11(2) plus T11(3] monoclonal antibodies. Interleukin 2 (IL-2) receptor expression and IL-2 production in mitogen-pulsed lymphocyte cultures was also investigated in parallel. DS cells responded poorly to all the blastogenic stimuli used in this study. Under certain experimental conditions (anti-CD3 or anti-CD2 antibody stimulation), the patients' lymphocytes expressed low levels of IL-2 surface receptors and failed to produce normal amounts of this lymphokine. Studies are currently in progress in our laboratories to determine whether these defects are due to an impairment of the early signalling events surrounding the complexing of CD3, CD2, or lectin receptors to their respective ligands.

Adolescent↗
PubMed1989

T-cell response to phorbol ester PMA and calcium ionophore A23187 in Down's syndrome.

The proliferative response of purified T cells to anti-CD2 monoclonal antibodies (T112 plus T113) was found to be markedly reduced in 12 subjects with Down's syndrome (DS). The addition of phorbol ester PMA, which activates Ca2+/phospholipid-dependent enzyme protein kinase C, or calcium ionophore A23187, which increases intracytosolic free Ca2+ concentration, enhanced, but did not normalize, the defective anti-CD2-mediated T-cell mitogenesis. In contrast, the proliferation of resting lymphocytes from trisomic patients was comparable to that of the control cells when PMA and A23187 were used as co-blastogenic reagents. Because PMA and A23187 together bypass the early activation pathways and promote T-cell growth through the direct induction of membrane interleukin 2 (IL-2) receptor expression and IL-2 synthesis and secretion, it could reasonably be hypothesized that the faulty DS T-cell activation induced by antigen or mitogen is due to a deranged transmembrane signal transduction, rather than a defect in the later intracellular events.

Adolescent↗
PubMed1989

Helper inducer T cells in the lungs of sarcoidosis patients. Analysis of their pathogenic and clinical significance.

Phenotypic analysis of helper CD4+TQ1- cell population, the major helper T-cell subset for B-cell responses, was carried out in BAL fluid of sarcoidosis patients. Most of the BAL CD4+ cells lacked TQ1 membrane antigen. A correlation between the number of helper CD4+TQ1- cells and IgM and IgA levels was observed in 27 sarcoidosis patients' BAL. A role of CD4+TQ1- cells in modulating lung B-cell immunoglobulin secretion in sarcoidosis was confirmed by the fact that BAL IgG level and helper T-cell number correlated well in patients with low-intensity alveolitis. Results showed an inverse correlation between symptom duration and BAL IgM levels and CD4+TQ1- cell number. The number of helper cells was above normal in patients who had symptoms for less than 12 months and within normal range in those who had symptoms for more than that. The pathogenic and clinical relevance of these data is discussed.

Adult↗
PubMed1989

Morphometric analysis of elastic fibers in human skin lymphatic capillaries.

In contrast to their absence near dermal blood capillaries, elastic fibers are commonly seen adjacent to dermal lymphatic capillaries under light microscopy. Based on morphometric analysis, the elastic fiber network that surrounds these skin lymphatic capillaries is predominantly oriented longitudinally to the lymphatic vessel wall. Quantitative analysis reveals that the density of these pericapillary elastic fibers are almost twice that of the intercapillary elastic fibers but only about one-half as thick. These data suggest that dermal lymph capillaries are surrounded by a specific elastic network of functional significance, morphologically distinct from that seen in the intercapillary dermis. Because lymphatic capillaries are often difficult to identify especially when collapsed, this elastic network may facilitate the positive identification of dermal lymphatic capillaries by light microscopy and thereby help differentiate them from blood capillaries. The possible role of this lymphatic elastic network in the absorptive activity of the dermal lymphatic system is also discussed.

Adolescent↗
PubMed1988

Increased density of perivascular nerves to the major cerebral vessels of the spontaneously hypertensive rat: differential changes in noradrenaline and neuropeptide Y during development.

Fluorescence and immunohistochemical techniques were used to study the pattern and density of perivascular nerves containing noradrenaline (NA) and neuropeptide Y (NPY) supplying the major cerebral arteries of 4-, 6-, 8- and 12-week-old spontaneously hypertensive rats (SHR) and normotensive Wistar (WIS) controls. Levels of NA and NPY in the superior cervical ganglia were measured. The density of nerves containing NA and NPY was greater in the hypertensive animals at all ages studied. However, the developmental changes in the density of innervation showed similar trends in both SHR and WIS groups. With few exceptions, there was a significant increase in the density of nerves containing NA from 4 to 6 weeks and from 8 to 12 weeks of age. This was in contrast to a low expression, and in some vessels a significant decrease in the number of NPY-containing nerves from 4 to 6 weeks. The density of nerve fibres containing NPY increased significantly in almost all vessels between 6 and 8 weeks of age and then stabilized. Thus there is a differential time course for the appearance of NA and NPY during development. Furthermore, the hyperinnervation of cerebral vessels in SHR by nerves containing NA and NPY precedes the onset of hypertension and associated medial hypertrophy. High-performance liquid chromatography and enzyme-linked immunosorbant assays show that the NA and NPY contents of the superior cervical ganglion do not reflect the changes in innervation pattern seen in the terminal fibres in the cerebral arteries. This tends to support the view that a local neurovascular mechanism is involved in the maintenance of hypertension. The possibility that increase in NPY as well as NA in cerebral perivascular nerves of hypertensive animals is involved in the protection of the blood-brain barrier against oedema and cerebral haemorrhage is raised.

Aging↗
PubMed1988

Identification of beta-adrenergic sensitive adenylate cyclase in rat thoracic duct.

The effect of L-isoproterenol on the 3',5'-cyclic adenosine monophosphate (cAMP) generating system in rat thoracic duct membranes was investigated in order to identify beta-adrenergic receptors. L-Isoproterenol elicited a dose-dependent stimulation of cAMP formation; L-noradrenaline was less effective than L-isoproterenol in stimulating cAMP increase, whereas L-phenylephrine was without important effects on cAMP levels. L-Propranolol, a selective antagonist of beta-adrenergic receptors, caused a dose-dependent decrease of the effects of L-isoproterenol. In contrast, the L-isoproterenol-elicited increase of cAMP was unaffected by the alpha-adrenergic and dopamine receptor-blocking agents phentolamine and haloperidol. These data indicate that L-isoproterenol stimulates cAMP formation in the rat thoracic duct by a specific interaction with beta-adrenergic receptors positively coupled to adenylate cyclase.

Adenylyl Cyclases↗
PubMed1988

The "switch-off" mechanism of spontaneous resolution of acute gout attack.

Urate crystal size change and the modification of coated proteins by oxygen radicals released by stimulated polymorphonuclear cells (PMN) could represent a likely "switch-off" mechanism of the spontaneous resolution of acute gout attack. The absorption spectra and the uric acid, allantoin and urea concentrations were determined before and after in vitro exposition of monosodium urate (MSU) crystals to superoxide anion (O2) photochemically generated. The results showed a complete dissolution of MSU crystals after incubation under O2-, with decrease of uric acid and increase of allantoin and urea concentrations. Our results were confirmed by polarizing, electron microscopy and calorimetric techniques. The results obtained seem to confirm that the spontaneous resolution of acute gout attack could be attributed to the dissolving effect on urate crystals and the modification of coated proteins by O2- released by phagocytizing PMN.

Acute-Phase Reaction↗