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Purpose This study aims to compare the accuracy of mean GH profile (GHP) Methods We retrospectively enrolled 100 acromegaly patients, 68 responder, and 32 partial responder to SRLs. Controlled disease has been defined as IGF-I levels within age-related normal limits, while partial response as pathological IGF-I values despite a reduction ≥ 50%. In all patients, GHP, SGH, IGF-I, and IGFBP-3 were evaluated. Results Median GHP levels (1.2 ng/ml, IQR 0.5–2.3 ng/ml) were lower (p = 0.001) than SGH (1.9 ng/ml, IQR 1.0–3.6 ng/ml). Accuracy of GHP was 81%, whereas that of SGH was 55%, with a Kappa index of 0.520 and 0.237, respectively. In multivariable analysis GHP (p = 0.002) and IGFBP-3 (p = 0.004), but not SGH, were independently associated with normal IGF-I levels. At receiver–operator characteristic curve (ROC) analysis GHP cut-off sensitivity and specificity were 94.1% and 50.0%, respectively, while SGH sensitivity and specificity were 35.3% and 93.7%, respectively. Finally, in obese patients the GH cut-off level (both as SGH and GHP) associated to good disease control was significantly different with respect to not obese ones. Conclusions GHP associates with IGF-I (and therefore with appropriate control of disease) with higher accuracy than SGH. When GH evaluation is needed, the measurement of mean GHP should be preferred and use of BMI-related cut-offs is suggested.

In patients with suspected acromegaly, evaluation of IGF-I is recommended as first-line test, while the assessment of GH-nadir during oral glucose tolerance test (OGTT) is advised as confirmatory test. The procedure of this test generally involves GH measurement every 30 min (30') from baseline to +120' or +180'. However, the optimal timing of samplings for the distinction between patients with or without active acromegaly is still a matter of debate.Sixty-seven healthy subjects and 46 acromegalic patients who achieved documented and persistent long-term cure were enrolled. A greedy algorithm was used to identify the minimal subset of time-points that sufficed to correctly detect GH suppression.The sampling at 90' was the one in which a GH level 1 μg/L was most frequently achieved (i.e., in 91.3% of cured acromegalic patients and in 91.0% of healthy subjects). Considering the whole cohort, the best combination of 2 time-points was +90' and +150' and achieved 95.6% accuracy; the best combination of 3 time-points was +60', +90' and +150' and achieved 99.1% accuracy. The minimal subset of GH determinations that demonstrated perfect accuracy (100%) needed the inclusion of 4 time-points, namely +60', +90', +120' and +150'.A subset of 4 time-points (60' - 90' - 120' - 150') was identified as the most relevant to detect GH suppression at OGTT, with a perfect classification of 100% of subjects. This supports the possibility to restrict the blood samplings to these time-points when assessing disease cure, with possible advantages in terms of saving time and lowering costs.

Bovine herpesvirus 4 (BoHV-4) is a gammaherpesvirus highly prevalent in the cattle population that has been isolated from the milk and the serum of healthy infected cows. Several studies reported the sensitivity and the permissiveness of some human cells to BoHV-4 infection. Moreover, our recent study demonstrated that some human cells sensitive but not permissive to BoHV-4 support a persistent infection protecting them from tumor necrosis factor- α –induced apoptosis. Together, these observations suggested that BoHV-4 could represent a danger for public health. To evaluate the risk of human infection by BoHV-4 through milk or serum derivatives, we investigated the resistance of BoHV-4 to the mildest thermal treatments usually applied to these products. The results demonstrated that milk pasteurization and thermal decomplementation of serum abolish BoHV-4 infectivity by inactivation of its property to enter permissive cells. Consequently, our results demonstrate that these treatments drastically reduce the risk of human infection by BoHV-4 through treated milk or serum derivatives.

Serum autoantibodies to fibrillin 1, the major component of microfibrils in the extracellular matrix, recently have been reported to occur in the tight skin mouse and in patients with systemic sclerosis, but not in patients with other connective tissue diseases. This study was undertaken to determine whether antifibrillin 1 antibodies could be detected in patients with localized forms of scleroderma.Sera from 50 patients with localized scleroderma (27 with linear scleroderma and 23 with morphea) and 51 normal controls were tested for IgG and IgM antifibrillin 1 autoantibodies, using a radioimmunoassay (RIA) and a human recombinant fibrillin 1 protein (rFbn-1).Both in patients with linear scleroderma and in those with morphea, mean levels of IgM and IgG binding to rFbn-1 were significantly higher than in controls. Eight patients with linear scleroderma (30%) and 6 patients with morphea (26%) had IgG autoantibodies to fibrillin 1 (rFbn-1) by RIA, compared with 3 controls (6%) (P = 0.006 and P = 0.022, respectively). No correlations between antifibrillin 1 antibodies and active skin disease or antinuclear antibody positivity were found.Autoantibodies to fibrillin 1 occur in patients with both forms of localized scleroderma (linear scleroderma and morphea). The clinical and pathogenetic significance of this autoimmune response remains to be determined.

The ministerial decrees of 15/4/94 and 14/12/94 defined the new payment schedules for hospital services during ordinary and day hospitalization; the hospital discharge form (SDO) is the main source of this information. The services are defined by the classification of ROD ("raggruppamenti omogenei di diagnosi"), adapted from the American DRG ("Diagnosis related groups"), which have substituted the traditional system of payment by production factor. On the basis of the DRG identified and the length of hospital stay, the Region pays the hospital the cost of hospitalization. The main diagnosis at discharge, secondary diagnosis, complications and diagnostic/therapeutic procedures all contribute to the determination of 489 DRG. Groups of pathologies are reclassified into 25 MDC ("Major Diagnostic Categories"). The 11th MDC includes the uronephrological DRG (302-333). The nephrological sector has been penalized by the inadequate value given to related procedures and diagnostic limitations. In order to guarantee efficacious diagnostic and therapeutic procedures, without impoverishing the nephrological budget and reducing the management autonomy of the divisions and autonomous services with hospitalization, it is necessary to introduce quality controls and corrective measures to the procedures that maintain the value of diagnosis and comply with financial considerations.

The authors present a case of idiopathic pulmonary fibrosis with an unusual onset in the form of acute interstitial pneumonia. On being admitted to hospital the 53-year-old woman presented an altered breathing pattern which initially required oxygen therapy using Venturi's oxygen mask followed by sedation and mechanical ventilation with appropriate FiO2 to guarantee adequate pO2 and arterial saturation. For diagnostic purposes bronchiolar and alveolar lavage was immediately performed together with transbronchial biopsy during the course of fibrobronchoscopy. The results of these tests revealed a syndrome of interstitial pneumonia and widespread alveolar lesion with an enhanced lymphocyte population. Antibac-terial and immunosuppressive therapy (6-methylprednisolone and cyclophosphamide) commenced on the basis of these tests caused a temporary improvement in blood-gas parameters and parenchymal thickening. But in spite of treatment the patient's cardiocirculatory and respiratory conditions deteriorated, causing death. This case report raises a number of different questions regarding both diagnosis and treatment. With regard to diagnosis it is worth underlining the absence of hyaline membrane, pathognomonic of widespread alveolar lesions, in biopsies removed while the patient was still alive. With regard to treatment, in addition to specific antibiotic and immunosuppressive therapy, the authors consider that surfactants might be of some help given that widespread alveolar damage can be attributed to pulmonary fibrosis.

The advent of genetic engineering has allowed for the expression and production of recombinant proteins carrying short immunogenic epitopes of foreign antigens. These antigenized molecules represent valuable tools to investigate the molecular basis of antigen fragmentation, generation and presentation of peptide to lymphocytes, the induction of epitope specific immunity and potentially the development of a new generation of vaccines. Recently, we expressed viral epitopes on immunoglobulin molecules by replacing the D segment of a variable region of the heavy chain (VH) gene with a B cell epitope from the V3-loop of HIV-1 envelope protein, as well as a cytotoxic T lymphocyte (CTL) and a T helper epitope from influenza virus nucleoprotein and hemagglutinin, respectively. The T cell peptides generated from the immunoglobulin molecules produced by cells transfected with chimeric V genes, activated specific T cells as they do when generated from viral proteins. Possible practical applications for the development of prophylactic and immunotherapeutic reagents are envisioned for immunoglobulin molecules bearing foreign epitopes.

Serum samples from 147 patients with different systemic autoimmune diseases (SLE, Sjögren's syndrome, and progressive systemic sclerosis) were tested for anti-Fc gamma R activity using mouse rFc gamma RII in an ELISA. High reactivity compared to normal individuals was found for patients with all three diseases. The anti-Fc gamma R antibody was purified from several serum samples by affinity chromatography on a Sepharose column coupled with denatured, murine rFc gamma RII. Both IgM and IgG antibodies were found. To analyze the specificity of the affinity-purified autoantibody, cells (human neutrophils, IFN-gamma-stimulated neutrophils, monocytes, and the THP-1 monocytic cell line) that express different combinations of Fc gamma R (CD64, CD32, CD16) were stained with the affinity purified Ig. Ig directed against all three types of Fc gamma R were found. The results may reflect on the role of Fc gamma R-specific antibodies in the pathology of autoimmune diseases.

Idiotypic vaccines are discussed in relation to those produced conventionally or those which are genetically engineered. The potential value of antiidiotypic antibodies as vaccines has been demonstrated in various animal models of infectious agents. These antibodies represent a heterogenous population: those which bear an internal image of the antigen and those which do not. These groups are discussed in terms of their immunochemical properties, relative frequencies and efficacy as vaccines. The infectious diseases in which antiidiotypic vaccines would be most useful are discussed, as well as problems which may be encountered in the use of such vaccines in humans. Some solutions to these problems are envisaged and an ideal idiotype vaccine is described.

Tetanus toxoid induced-blast transformation of peripheral blood lymphocytes of 15 immunized healthy subjects was studied. According to the magnitude of the [3H]thymidine incorporation, the subjects were classified into two groups: high and low blast specific responses. The high or low blast response induced by tetanus toxoid did not correlate with the stimulation induced by PHA and PPD nor with the antitetanus-antibody titer of these subjects. T cells were shown to be involved in this specific blast response. The differences in the magnitude of the blast response could be easily explained by the existence of B cells with suppressor activity on T cells functions rather than by inhibition of the tetanus toxoid induced stimulation by an antigen-antibody complex. Relationship with HL-A system will be investigated.

51 biopsies of tibial growing cartilage were performed in children with and without growth disturbances. The biopsy procedure is described. The clinical and roentgenological follow up did not reveal any untoward effects due to the operation. The histological and cyto-enzymological methods used in the study of the biopsies as well as the main results obtained are presented and discussed. In a few cases the effect of a growth stimulating treatment could be studied by means of a repeated biopsy from the opposite leg.

Nocardia-delipidated cell mitogen (NDCM), a particulate fraction prepared from Nocardia opaca, is able to stimulate the proliferation of small resting human B lymphocytes and their differentiation into Ig-secreting cells. This fraction contains two active structures: the cell wall peptidoglycan (PG) and a fraction (Cy I) derived from the cytoplasmic compartment. Treatment of insoluble PG with various bacteriolytic enzymes showed that the minimal structure required for mitogenic activity is more complex than that required for the differentiation of human lymphocytes. The mitogenic activity of cell wall fractions varies in different bacterial species; that prepared from N. opaca is the more potent. Both mitogenic structures of N. opaca induce higher responses in infant and adult PBL as compared to cord lymphocytes. The differentiation of B lymphocytes into Ig-secreting cells induced by PG fractions is T-dependent.

The lymphocytes are coated by an external glycoprotein layer the so-called cell coat. There is some difference between the structure of the cell coat of T- and B-derived lymphocytes. The cell coat represents the chemical basis of some lymphocytic properties, i.e. their homing and electrophoretic mobility and it plays and important role in the expression of antigenicity of lymphocytes and the triggering of blast transformation.

Five cell lines were isolated after prolonged culture of human buffy coat leukocytes. The cells consisted for the most part of lymphoblasts morphologically similar to those produced by in vivo or in vitro stimulation of small lymphocytes by antigens or mitogens. One of the lines possessed virus-like particles of the Epstein-Barr type. All the established lines were capable of mediating antibody-dependent cytotoxicity (LADC) quantitatively at a level not significantly different from that mediated by freshly isolated, normal human peripheral blood lymphocytes (PBL). The LADC of the lymphoblasts was inhibited by all the human IgG subclasses tested (IgG1, IgG2, IgG3, IgG4) as was the LADC of PBL. It is concluded that, at least so far, the lymphoblasts have retained the properties of the lymphocytes from which they were originally derived as regards their ability to mediate LADC.

Specific stimulation of thymus-derived cells by purified protein derivative or tetanus toxoid was inhibited by autologous lymphocytes. The lymphocytes, which were collected from healthy humans who had been vaccinated with bacille Calmette-Guerin were purified on nylon columns after removal of cells that form rosettes with sheep erythrocytes. The degree of purification of the lymphocytes was controlled by appropriate techniques.

Macrophage inhibition factor (MIF) like substances were found in the supernatants of human lymphoid cultures stimulated by concanavalin A, tuberculin and allogeneic lymphocytes. These agents are usually regarded as elective stimulators of T lymphocytes. No such a phenomenon was shown when lymphocytes were stimulated by lipopolysaccharide or by goat anti-human F(ab')2 serum, which are known as preferential B-cell stimulators.

We have dissected the human influenza-specific B cell repertoire by performing Epstein-Barr virus (EBV) limiting dilution analysis of lymphocytes obtained from donors before and after immunization with a commercially available influenza vaccine. In addition to an analysis of precursor frequency and light chain diversity, we studied sera and culture supernatants containing human anti-influenza antibodies with a panel of murine monoclonal antibodies specific for idiotopes identified on murine anti-PR8 and anti-X-31 antibodies. An idiotypic specificity present on the X-31-specific murine monoclonal PY206 has previously been shown to be shared by murine antibodies specific for PR8, X-31, and other influenza viruses. We observed little correlation among the following parameters: anti-viral titer, serum idiotope content, precursor frequency and immune status. More interestingly, there was a striking predominance of human influenza-specific antibodies that utilized lambda light chains. In addition, 12 of 26 human anti-influenza monoclonals strongly inhibited the binding of one of the murine anti-idiotopes to the labeled murine antibody, PY206. This is the same idiotope that is shared among murine antiinfluenza antibodies and all six individuals studied contained clones reactive with this anti-idiotope. Seven of these 12 idiotope-positive human antibodies gave partial cross-reactivity in a second anti-idiotypic system. These observations imply that a significant level of homology exists between the binding sites of human and murine influenza-specific antibodies and suggest that idiotypic manipulation of the human immune response to influenza virus may have important therapeutic implications.

Immunization of humans with tetanus toxoid (TT) results in an inhibition of the reactivity of peripheral lymphocytes to TT as well as to one-way mixed lymphocyte reaction. The strongest inhibition was observed in cells taken 3 or 7 days after immunization. These reactivities reappeared on the 14th day and reached their initial levels by the 21st day after immunization. The role of the various cell types was studied by culturing separately purified T or B lymphocytes taken on day 7 after immunization. B cells alone are not stimulated by TT or allogeneic cells. Purified T cells are stimulated much more than the initial total cell population. When B cells were mixed and cultured along with T cells, a suppressor effect upon stimulation appeared which reduced 3H-thymidine incorporation to the levels of the initial population. Treatment with 5-bromodeoxyuridine followed by exposure to light of cells stimulated with TT abrogated their ability to respond to subsequent stimulation with TT; whereas the responsiveness of treated cells to allogeneic lymphocytes was not significantly affected and vice versa. These results suggest that each stimulator activated a separate population of T cells but that in vivo immunization provoked the development of both a specific and nonspecific suppressor activity. Most probably this suppressor activity was brought about by adherent, surface Ig-bearing (B) cells.

Histochemical investigations were performed on biopsies of human tibial growing cartilage, in normal and pathologic conditions; (Hurler and Turner's syndrome, pituitary dwarfism, Pairbank's disease and Morquio disease, achondroplasia, Cornelia de Lange dwarfism, pseudoparathyroidism). The distribution of the glucosidic component appears to be different as compared to the normal cartilage. The distribution of acid mucopolysaccharides in normal cartilage and changes occuring in various disorders of growth, indicate the important part that mucopolysaccharidic components of the matrix are playing in the process of growth and calcification.