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While vaccines are effective in adults, they are less successful in newborns and infants. Neonatal unresponsiveness to vaccines could be owing to immaturity of lymphocytes and/or to inhibition by maternal antibodies. Unresponsiveness of newborn to vaccines can be overcame by genetic immunization. In the present study we investigated the effect of maternal antibodies on the anti-influenza virus protective response in progeny born to dams immunized with plasmid containing the hemagglutinin gene or UV-inactivated virus. The effect of maternal antibodies was studied in plasmid immunized F1 mice born to BALB/c dams, previously immunized with virus or plasmid and crossed with C57BL/6 males, as well as in offspring born to BALB/c dams immunized with plasmid and then immunized with UV-inactivated WSN virus. We have found that the inhibition period of the anti-HA antibody response in offspring born to dams immunized with DNA is shorter than that of offspring born to dams immunized with virus. Furthermore, there is a persistent inhibitory effect on B cells from offspring born to dams immunized with virus or injected with antiviral monoclonal antibodies (MoAb), after the decline of maternal antibody titers. The analysis of the haemagglutinin-specific clonotype reactivity pattern of offspring born to dams immunized with inactivated influenza virus or with a plasmid showed that clonotypes producing antibodies specific for the immunizing virus strain were predominant in offspring born to dams immunized with DNA compared to those born to dams immunized with virus. Maternal antibodies do not affect cell-mediated immunity. These findings might be used to design efficient vaccination schedules for newborns and infants.

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.

Nas sementes de leguminosas é comum a ocorrência de dormência devido à dureza do tegumento. Sementes de bordão-de-velho (Samanea saman (Jacq.) Merr.), angico-de-bezerro (Piptadenia moniliformis Benth.), pau-ferro (Caesalpinia ferrea Mart. ex. Tul.) e sabiá (Mimosa caesalpiniifolia Benth.) foram submetidas aos seguintes tratamentos: escarificação com lixa, água a 80ºC por 1,0; 2,5 e 5,0min; água à temperatura ambiente (12; 24 e 48h); ácido sulfúrico concentrado (1; 5 e 10min) e álcool etílico (5; 10 e 25min), visando a quebra da dormência. De sabiá foram testados os artículos e as sementes nuas. Usou-se o delineamento inteiramente ao acaso, com quatro repetições (50 sementes/repetição). Os tratamentos com ácido sulfúrico resultaram em maiores percentuais de germinação para bordão-de-velho (98,5-99,0%) e para pau-ferro (76,5-89,0%). Para angico-de-bezerro, destacaram-se água a 80ºC durante 1,0 ou 2,5min, e ácido durante 10min (82,5; 74,0 e 87,0% de germinação, respectivamente). Maiores percentagens de germinação foram obtidas nas sementes nuas de sabiá do que nos artículos, destacando-se, com germinação de 73,0 a 93,5%, os tratamentos com água a 80ºC, com ácido 5 e 10min, e com álcool etílico por 5min. Considerando-se o custo e os riscos na utilização do ácido sulfúrico, é preferível, para quebrar a dormência das sementes estudadas, a utilização dos tratamentos com água a 80ºC, ainda que seja necessário aumento na densidade de semeadura. In legume seeds dormancy imposed by the hard seed coat is common. Seeds of four legumes, Samanea saman (Jacq.) Merr., Piptadenia moniliformis Benth., Caesalpinia ferrea Mart. ex. Tul., and Mimosa caesalpiniifolia Benth. were scarified with sand paper; hot water (80ºC) for 1, 2.5 and 5.0 min; water at room temperature for 12, 24 and 48h; concentrated sulphuric acid for 1, 5 and 10 min; and in ethilic alcohol for 5, 10 and 25 min, to break seed coat dormancy. In M. caesalpiniifolia the treatments were applied to both articule and naked seeds. A completely randomized experimental design with four replications (50 seeds/ replication) was used. The treatments with sulfuric acid were the most effective on S. saman (98.5-99.0% germination) and C. ferrea (76.5-89%). For P. moniliformis, germination was best achieved after the application of hot water (1 or 2.5 min) and sulphuric acid during 10 min (82.5, 74 and 87% germination, respectively). For M. caesalpiniifolia, the results with naked seeds were better than with articules, the hot water, sulphuric acid (5 and 10min), and ethilic alcohol (5min) treatments being especially effective, with germination ranging from 73% to 93.5%. Due to the costs and risks when using sulphuric acid, it would be recommended the use of hot water treatments, even if some increase in sowing density becomes necessary.

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 possible role of silicone in the pathogenesis of a scleroderma-like syndrome is still unresolved. It has been proposed that silicone escaping from breast implants potentiates the progression of the disease. To clarify whether silicone enhances development of fibrotic skin lesions and autoantibodies, we tested its effect on tight skin (TSK/+) mice. TSK/+ mice spontaneously develop skin fibrosis and characteristic autoantibodies which resemble human scleroderma. The results of the present study indicate that silicone administration does not enhance development of skin fibrosis nor synthesis of autoantibodies to RNA polymerase and topoisomerase in TSK/+ mice.

The possible role of silicone in the pathogenesis of a scleroderma-like syndrome is still unresolved. It has been proposed that silicone escaping from breast implants potentiates the progression of the disease. To clarify whether silicone enhances development of fibrotic skin lesions and autoantibodies, we tested its effect on tight skin (TSK/+) mice. TSK/+ mice spontaneously develop skin fibrosis and characteristic autoantibodies which resemble human scleroderma. The results of the present study indicate that silicone administration does not enhance development of skin fibrosis nor synthesis of autoantibodies to RNA polymerase and topoisomerase in TSK/+ mice.

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.

Various immunologic functions of rabbit lymphocytes were studied during ontogeny. Liver cells of 17-day-old fetuses responded to concanavalin A and only after 22 days responded to phytohemagglutinin. The thymus cells of 22-day-old fetuses and the spleen cells of 29-day-old fetuses were stimulated by concanavalin A but not by phytohemagglutinin. The response to phytohemagglutinin in thymus and spleen cells was obtianed only after the birth. These results suggest that, in the rabbit, there are different subsets of T lymphocytes that respond either to concanavalin A or phytohemagglutinin. An alternative hypothesis is that the receptor for concanavalin A and the receptor for phytohemagglutinin appear on the same cells at different stages of the development. No stimulation of fetal liver was obtained with B mitogens, i.e., Nocardia water soluble mitogen (NWSM) and antisera against allotypes of the b series whereas neonatal spleen cells were stimulated. These results indicate that the ability of lymphocytes to respond to a nonspecific rabbit B cell mitogen, namely NWSM, and to a specific rabbit B cell mitogen, namely anti-allotypic antibody, matured only in peripheral lymphoid organs, such as spleen, in spite of the fact that these two mitogens stimulate different subsets of B lymphocytes. Significant synthesis of immunoglobulins by liver cells was obtained in 22-day-old fetuses. The liver cells possessed Fc receptors after 17 days of gestation and a significant antibody dependent cell-mediated cytotoxicity after 22 days. Both functions decreased after birth in these cells. These results showed a sequential acquisition of immunologic functions of rabbit lymphocytes.

An idiotype of the dinitrophenyl-binding myeloma protein MOPC 460 was expressed on a small but significant proportion of anti-TNP antibodies which appeared after in vivo or in vitro immunization of BALB/c mice with three T-independent TNP antigens. In vitro experiments show that the depletion of T cells before culture increased significantly the number of plaques secreting anti-TNP antibodies bearing MOPC 460 idiotype (460Id). T cells from BALB/c mice, but not from C.B20 mice, exhibit this suppressor activity. Plate-binding experiments indicate that the suppressive action of the T-lymphocyte population depends on a cell which can bind to MOPC 460 myeloma protein. The possible role of these normally occurring, idiotype-specific T cells on expression of 460Id in the anti-TNP antibody response of BALB/c mice is discussed.

Two purified peptidoglycans extracted from E. coli or B. megaterium strongly stimulated the spleen lymphocytes of rabbits and of normal or nude mice. Both preparations can substitute for Mycobacteria in Freund's complete adjuvant. The peptidoglycan extracted from M. lysodeikticus by a similar procedure which lacks adjuvant activity, did not induce blast transformation. However, the monomere of the E. coli peptidoglycan was devoid of mitogenicity although it has also a marked adjuvant activity.

A relativistic quantum-mechanical formalism is constructed, and it is shown that it is suitable to describe the scattering states of an isolated system of two interacting scalar particles. This formalism is applied to the electromagnetic interaction, and it gives an expression for the differential cross section which is a generalization of the Rutherford formula.

The B-cell mitogens lipopolysaccharide (LPS), Nocardia water-soluble mitogen (NWSM), and dextran sulfate (DxS) react with different subpopulations of B lymphocytes. Selective in vitro killing of cells responding to either LPS or NWSM has little effect on the in vitro response to the other mitogen, although the response to DxS is reduced in both cases. If, after selective in vitro killing, cells are injected into irradiated mice for 2-3 wk before measuring their in vitro mitogen responses, the same specificity pattern is seen. Thus, one is dealing with different B-cell subpopulations rather than different stages of maturation of a single population. Treatment with various alloantisera and complement before measuring the mitogen response to LPS and NWSM shows that (a) whereas all LPS response cells carry surface Ig, a subpopulation of NWSM responsive cells does not; (b) both LPS- and NWSM-responsive cells carry I-A antigens but might not I-E or I-J antigens; (c) all LPS-responsive cells carry I-C antigens, whereas approximately 25% of NWSM responsive cells do not: (d) there is a subpopulation of NWSM-responsive cells carrying neither surface Ig nor I-C antigens and resistant to anti-theta treatment.

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.

The antibody response of normal adult, of young and of nu/nu BALB/c mice to bacterial levan was characterized in terms of its relative specificity for levan and for inulin and of the expression of a family of cross-reactive idiotypes (IdX) found on BALB/c myeloma proteins which bind inulin and levan. Normal adult BALB/c mice immunized with levan develop prompt antibody responses which can be detected by serum hemagglutinin assays or by enumeration of plaque-forming cells. These antibodies are specific for levan and many also bind inulin. In addition, the IdX is expressed on a substantial fraction of the anti-levan antibodies, particularly those that bind both inulin and levan. The response to levan is thymus independent in that nu/nu BALB/c mice and lethally irradiated BALB/c mice reconstituted only with bone marrow cells produce anti-levan antibodies. However, the response of nu/nu BALB/c mice to levan is unusual in that the titer of anti-inulin antibodies and of serum IdX is very low. When young mice (2 to 4 weeks of age) are immunized with levan they respond quite well, but their anti-levan antibodies also fail to bind inulin or to express the IdX. These results suggest that the unusual specificity of the response of nu/nu BALB/c mice may reflect the need for a functional thymus in the normal maturation of the thymus-independent lymphocytes which respond to levan with the secretion of antibodies that bind inulin and express the IdX. Finally, cells secreting antibodies specific for the IdX are regularly observed in the spleens of mice immunized with bacterial levan. This is consistent with regulation of the anti-levan response by autoanti-idiotype antibodies.

Syngeneic anti-(anti-Id) antibodies were prepared against BALB/c anti-A48Id antibodies, BALB/c anti-460Id monoclonal antibodies, and A/J anti-J558 IdI monoclonal antibodies. With these anti-(anti-Id) antibodies we identified cross-reactive idiotypes on syngeneic and homologous anti-A48Id and anti-460Id antibodies. By contrast, tbe idiotypic determinants of A/J anti-J558 IdI monoclonal antibodies were not shared by other syngeneic, homologous, or xenogenic anti-J558 IdI or IdX antibodies. These results suggest that idiotype-antiidiotype reactions that serve as regulatory controls within the immune system are characteristic for each particular antigen system, strain, or species and that such interactions make the system self-limited with respect to the whole antild repertoire.

A water-soluble extract of Nocardia opaca (NWSE) induced a very strong stimulation of rabbit and mouse spleen lymphocytes and a weak, but significant, increase of thymidine incorporation by human peripheral lymphocytes and monkey blood, or spleen cells. As was demonstrated by the migration inhibition factor assay, the strong mitogenic activity observed with mice spleen cells was not related to a state of natural impregnation. In the same experiments, the various lymphocytes were also incubated with M. smegmatis water-soluble adjuvant (WSA) and S. enteritidis lipopolysaccharide (LPS). No mitogenic activity was shown with WSA even when this extract was incubated with the lymphocytes of human tuberculin responders, showing that this preparation is free of tuberculoprotein contaminants. Finally, it must be noted that, contrary to what is observed in mice, LPS did not induce thymidine incorporation by monkey or rabbit spleen cells.

Lymphoid cells bearing Fc receptors are able to lyse antibody-coated animal target cells in an antibody-dependent cell-mediated cytotoxicity reaction. The results presented here show that liposomes consisting of sphingomyelin, cholesterol, and cardiolipid and coated by cardiolipidic antibodies could be destroyed by spleen or thymus cells. No alteration of liposomes was observed when normal rabbit serum was used or when the effector cell population was depleted of cells bearing Fc receptors. The lysis of antibody-coated liposomes by effector cells could be carried out in two steps. In the first step, the fixation of antibodies on the cardiolipidic antigens could lead to a reorganization of the liposomal membrane. In the second step, the effector Fc-receptor-bearing cells might amplify this alteration of the liposomes.

Nocardia water soluble mitogen (NWSM) is known to stimulate mouse and rabbit lymphoid cells and to act selectively on murine B-derived lymphocytes. In this paper, evidence is presented that NWSM is also a mitogen for rabbit bursal equivalent cells and does not bring about blast transformation of thymus-derived rabbit cells. Pretreatment of rabbit spleen lymphocytes with antibody directed against rabbit thymus lymphocyte antigen (anti-RTLA serum) and with complement did not affect the strong increase of thymidine incorporation which follows stimulation with NWSM. The mitogen-induced polyclonal activation of antibody-forming cells and resulted in the presence of 30% of cells with the ultrastructural characteristics of plasmocytes. These observations led to the conclusion that NWSM is a mitogen for a B-derived lymphocyte of the rabbit.

Several idiotypic (Id) specificities have been identified by immunofluorescence on the membranes of B cells in the spleens of nonimmune mice. These determinants are displayed at frequencies varying from 0.22 to 1.83% of B cells and are entirely immunoglobulin (Ig) in nature. No Id determinants were observed on the membranes of four Slg- Abelson virus-transformed pre-B cell lines that are sensitive to LPS. Under our experimental conditions, we did not observe a significant increase in 3H-thymidine incorporation subsequent to the in vitro incubation of splenic lymphocytes from normal mice with various amounts of anti-Id antibodies specific for several cross-reactive (IdX) or individual Id. Similarly, in utero exposure to anti-Id antibodies against myeloma proteins specific for T-independent antigens displaying B cell mitogenic properties did not alter the proliferation of lymphocytes induced by these mitogens. In contrast, exposure to anti-Id antibodies in vitro as well as in utero had a profound and specific effect on the corresponding antibody responses and maturation of small lymphocytes into plasma cells. When normal B cells were cultured with the B cell mitogen LPS in the presence of anti-Id antibodies directed against the J558IdX, specific suppression of the maturation of IdX+ plasma cells was observed. In mice exposed to maternal anti-Id in utero, we observed a severe inability to mount an immune response to any compound that elicited antibody molecules bearing the Id that was complementary to the maternal anti-Id. These same maternally Id-suppressed mice, however, gave a normal response when the same compound was presented as a mitogen. Our results reinforce the concept that Id on membranes of B lymphocytes are associated only with Ig receptors and do not support the possibility of mitogen-like poly-clonal stimulatory properties of anti-Id antibodies.

A constant curvature synchronization is a foliation of the space‐time by spacelike hypersurfaces which are spaces of constant curvature for the induced metric. The classification of the space‐times admitting such a synchronization is given according to the dimension and structure of all the isometry groups that can act with orbits tangent to it.