PubMed Health⌕ Search

Biomedical subjects

T Cavallo

Publications and source records attributed to T Cavallo.

At least 37 records · Page 2Linked to original sources
PubMed1993

[Measurement of the spontaneous growth hormone increase in short children. Diagnostic significance and neuroendocrine implications].

The assessment of growth hormone deficiency (GHD) in children with growth retardation is frequently difficult. The diagnostic reliability of standard pharmacological GH provocative tests has been questioned and several investigators have focussed on measurement of spontaneous GH secretion at frequent intervals over periods of 12-24 hours, with mathematical analysis of resulting secretory patterns. The aim of our study was to assess GH secretion in children with growth retardation, either in prepuberal and puberal ages, in order 1) to evaluate the diagnostic relevance of spontaneous GH secretion in comparison to tests, and 2) to gain neuroendocrine interpretations of GH secretion. We investigated 58 short children (height < 5th centile), 35 males, aged 6.4-15 years, without chronic diseases or dysmorphic syndromes. All subjects were divided into 3 groups, either in prepubertal and pubertal ages: normal (normal growth rate, within -0.80 HVSDS; normal GH peak after standard clonidine test > 7 ng/ml; 15 prepubertal, 8 pubertal); slow-growing (growth rate lower than -0.80 SDS; normal GH peak to test; 13 prepubertal, 13 pubertal); GH deficit (growth rate lower than -0.80 SDS; GH peak to test < 7 ng/ml; 6 prepubertal, 3 pubertal). In all children spontaneous GH secretion was evaluated for 24-hrs, 12-hrs daily and 12-hrs overnight, sampling every 30 minutes. The results were analyzed by the PULSAR computer program to determine number, height, area and amplitude of pulses and the baseline and GH secretory areas under and over baseline.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Autoimmunity, polyclonal B-cell activation and infection.

It is widely believed that autoimmunity is an integral part of the immune system, and that genetic, immunologic, hormonal, environmental and other factors contribute to the pathogenesis of autoimmune disease. Thus, autoimmune disease may represent an abnormal expression of immune functions instead of loss of tolerance to self, and it can be organ specific or systemic in its manifestations. We review the various factors that contribute to the development of autoimmune disease; we also review the mechanisms of polyclonal B-cell activation, with emphasis on the role of infectious agents. We consider systemic lupus erythematosus in humans and in experimental animals as prototypic autoimmune disease, and we summarize data to indicate that polyclonal B-cell activation is central to the pathogenesis of systemic autoimmune disease. The effect of polyclonal B-cell activation, brought about by injections of a B-cell activator-lipopolysaccharide from Gram-negative bacteria-is sufficient to cause autoimmune disease in an immunologically normal host. In fact, autoimmune disease can be arrested if excessive polyclonal B-cell activation is suppressed; alternatively, autoimmune disease can be exacerbated if polyclonal B-cell activation is enhanced. We explore the mechanism of tissue injury when autoimmune disease is induced or exacerbated, and we consider the pathogenic roles of autoantibodies, immune complexes, complement, the blood cell carrier system, and the mononuclear phagocyte system. Although polyclonal B-cell activation may be the mechanism whereby various factors can cause or exacerbate systemic autoimmune disease, polyclonal B-cell activation may cause autoimmune disease on its own.

Animals↗
PubMed1992

Bacterial lipopolysaccharide causes variable deposits of diverse immunoglobulin isotypes in kidneys of lupus-prone mice.

We investigated the role of immunoglobulin isotypes in the exacerbation of lupus nephritis associated with exposure to bacterial lipopolysaccharide. The data indicate that enhanced polyclonal B-cell activation and exacerbated autoimmune disease evoked by lipopolysaccharide are associated with an increase in the concentration of isotypes in plasma and in renal eluate, that this isotype response is polyclonal and preferential but not restrictive, that all B cells are responsive but all are not equally sensitive to the effects of lipopolysaccharide, and that some expanded isotypes may be more nephritogenic in certain strains of lupus-prone mice.

Animals↗
PubMed1991

Fibrillary (immunotactoid) glomerulopathy. A possible role for kappa light chain in its etiology and/or pathogenesis.

The initial clinical manifestations, course, and immunopathologic findings of renal biopsies of nine patients with fibrillary glomerulopathy are reported. Their first symptoms and courses were variable, but proteinuria and renal failure were common. While some patients required hemodialysis soon after coming for treatment, others progressed to renal failure over several years. Three patients had monoclonal gammopathy; one of them had an isolated, transient, Bence-Jones proteinuria. The main pathologic features are glomerular enlargement, mesangial expansion, and mild hypercellularity. Congo red and thioflavin stains were negative. Kappa chain, either alone or with lambda chain and IgG, were the predominant immunoreactants. Ultrastructurally, the presence of coarse fibrils of 15-25 nm was characteristic, but there were also granular deposits in the capillary wall that occurred in a band-like pattern in the inner half of the glomerular basement membrane in a manner similar to the deposits seen in light chain deposit disease. The immunofluorescence and ultrastructural findings suggest that light chains (especially kappa) may be significant in the pathogenesis of fibrillary glomerulopathy and that there may be a relationship with light chain deposit disease.

Adult↗
PubMed1991

Bacterial lipopolysaccharide enhances deposition of immune complexes and exacerbates nephritis in BXSB lupus-prone mice.

Systemic autoimmune disease is influenced by genetic, immunological, hormonal, and environmental factors. Although environmental factors are major agents that induce or exacerbate autoimmune diseases, the mechanism(s) and the molecular events by which they operate remain poorly understood. Here we used the lupus-prone BXSB mouse as an animal model of systemic autoimmune disease, and we used a bacterial lipopolysaccharide (LPS) as a surrogate infectious agent to gain some insight into the mechanism(s) by which infectious agents exacerbate autoimmune diseases. Our experimental protocol was designed to address three questions: (i) whether spontaneous polyclonal B cell activation (PBA) that occurs in BXSB mice could be further enhanced by bacterial LPS; (ii) whether repeated exposure to LPS would exacerbate autoimmune disease, as reflected by enhanced deposits of immune complexes (ICs) in kidneys and exacerbated nephritis; and (iii) whether the mechanism by which LPS exacerbates nephritis might involve interference with blood cell carrier function, mononuclear phagocyte function, or both. BXSB mice were injected with LPS (25 micrograms) twice a week for 5 weeks; control autoimmune BXSB mice and immunologically normal (C57BL/6) mice were injected with vehicle only. The three groups of mice were then challenged with soluble ICs to assess the kinetics of their disappearance from the circulation, their uptake by the mononuclear phagocyte system (liver, spleen), their distribution in target organ (kidney), and blood cell carrier function. The results indicate that: (i) spontaneous PBA can be enhanced further by LPS; (ii) exposure to LPS results in increased deposits of endogenous ICs in kidneys and exacerbated nephritis; and (iii) defective handling of ICs by the mononuclear phagocyte system and impaired blood cell carrier function are contributory factors to exacerbated nephritis, but that mechanisms in addition to passive localization of ICs may also be operative.

Animals↗
PubMed1991

Bacterial lipopolysaccharide induces long-lasting IgA deficiency concurrently with features of polyclonal B cell activation in normal and in lupus-prone mice.

Polyclonal B cell activation (PBA) and autoimmune disease can be induced in immunologically normal mice, or enhanced in lupus-prone mice, by bacterial lipopolysaccharide (LPS). Because immune defects are common in autoimmune diseases and IgA deficiency is prevalent in patients with systemic lupus erythematosus, we investigated: (i) whether LPS might induce IgA deficiency in normal mice; (ii) whether IgA deficiency might be a feature in lupus-prone mice; (iii) whether, if present in lupus-prone mice, IgA deficiency could be further accentuated by LPS; and (iv) whether the effects of LPS on IgA concentrations of normal and lupus-prone mice might be reversible upon withdrawal of LPS. We injected normal (C57BL/6) and lupus-prone (NZB/W) mice with 50 micrograms of LPS from Salmonella minnesota Re595 twice a week for 5 weeks and then discontinued LPS for 6 weeks. We determined the concentrations of plasma immunoglobulins, DNA antibodies, and circulating immune complexes before, during, and after mice were exposed to LPS. Our results indicate that: (i) LPS induces IgA deficiency in normal mice concurrently with PBA; (ii) IgA deficiency is a feature of lupus-prone mice; (iii) LPS accentuates naturally occurring PBA and IgA deficiency in lupus-prone mice; and (iv) LPS induced, or LPS enhanced, IgA deficiency and PBA in normal and lupus-prone mice persist long after withdrawal of LPS. Thus, LPS triggers or enhances autoimmune disease by a mechanism that involves in part PBA with selective increase (IgG, IgM) and concurrent decrease (IgA) of specific isotypes.

Animals↗
PubMed1991

Antigen as mediator of glomerular injury in experimental IgA nephropathy.

IgA immune complexes (IgA-IC) are considered the primary cause of IgA nephropathy. Despite the consistent findings of IgA and frequently C3 glomerular deposits in most patients, the renal histopathologic lesion may vary from mild mesangial involvement to severe sclerosis. In the IgA immune deposits, IgA and C3 are considered to be relatively constant, whereas the composition of the antigen is expected to vary according to its origin. This report explored th possibility that the histopathologic lesion is a function of the antigen in an IgA immune deposit. To test this hypothesis we developed a passive model of IgA nephropathy whereby glomerular IgA deposits can capture, in situ, circulating antigens. In this model, glomerular IgA deposits (IgA/IgA-IC) were induced by administration of a constant amount of IgA anti-dinitrophenyl (antibody) and dinitrophenyl-conjugated IgA anti-phosphorylcholine (PC) as an antigen. The latter also served as antibody to capture, in situ, circulating PC-containing antigens. Mice that received only IgA/IgA-IC developed glomerular IgA and C3 deposits and a focal increase in mesangial cells and matrix, but no evidence of renal damage. A diffuse increase in mesangial cells and matrix developed in mice treated with IgA/IgA-IC and either PC-Ficoll (carbohydrate antigen) or PC conjugate of bovine serum albumin (protein antigen). In contrast, mice that received IgA/IgA-IC and pneumococcal C polysaccharide, a PC-containing antigen, developed severe diffuse mesangial hypercellularity with segmental necrosis and thrombosis. These mice also developed proteinuria and hematuria. Our results demonstrate that the antigen plays a critical role in development of glomerulonephritis associated with IgA-IC.

Animals↗
PubMed1990

Repeated exposure to bacterial lipopolysaccharide interferes with disposal of pathogenic immune complexes in mice.

Patients with systemic lupus erythematosus (SLE) experience clinical flares in association with superimposed bacterial infection. To investigate whether heightened immune phenomena during the course of bacterial infections were related to abnormal disposal of immune complexes, we administered bacterial lipopolysaccharide (LPS) to C57BL/6 mice for 5 weeks. Control mice received vehicle only. We then challenged the mice with a subsaturating dose of radiolabelled immune complexes intravenously and determined the localization of immune complexes in liver, spleen and kidney. In comparison to control mice, mice exposed to LPS developed features of polyclonal B cell activation, autoimmune phenomena, delayed removal of immune complexes from the circulation, diminished liver uptake of immune complexes, and enhanced localization of immune complexes in the kidneys. The findings could not be attributed to biological processes dependent on complement concentration. Instead, interferences with Fc receptor function, or with endocytosis of immune complexes may represent likely possibilities. Thus, clinical flares in patients with SLE, in the presence of a superimposed infection, may result from enhanced localization of immune complexes in organs due to altered mechanisms of their disposal.

Animals↗
PubMed1990

Prolonged circulation of immune complexes due to various altered immune functions contributes to nephritis in MRL/lpr mice.

To gain some insight into the pathogenesis of proliferative lupus nephritis in MRL/lpr mice we investigated the kinetics of removal of immune complexes from the circulation, the carrier state of blood cells, the uptake of complexes by the mononuclear phagocyte system, and the localization of complexes in kidneys. In nephritic MRL/lpr mice challenged with a subsaturating dose of radiolabelled complexes (2.5 mg bovine serum albumin-anti-bovine serum albumin) liver uptake was profoundly decreased, removal of circulating complexes was delayed, and 12-h kidney localization of complexes was enhanced 7.3-fold, in comparison to control mice. The findings were not encumbered by differences in complement concentration and most likely are attributable to various altered immune functions: spontaneous polyclonal activation of B cells, enhanced production of endogenous immune complexes, delayed removal of complexes from the circulation, and decreased uptake of complexes by the mononuclear phagocyte system. In concert, such altered functions contribute to prolonged circulation of complexes to result in their enhanced deposition in the microcirculation.

Animals↗
PubMed1990

Lipopolysaccharide from gram-negative bacteria enhances polyclonal B cell activation and exacerbates nephritis in MRL/lpr mice.

Depletion of B cells in mice bearing the lymphoproliferation (lpr) gene reduces lymphoproliferation and polyclonal B cell activation (PBA) and attenuates mononuclear cell vasculitis. We sought to verify whether the obverse was true, i.e. whether enhancement of B cell activity might exacerbate the nephritis of MRL/lpr (MRL) mice, a lupus-prone strain. The experimental approach was designed to address three questions: whether naturally occurring PBA in MRL mice could be further enhanced; whether enhanced PBA would exacerbate nephritis; and whether the mechanism of nephritis exacerbation involved interference with mononuclear phagocyte system (MPS) function. To enhance B cell activity, we injected MRL mice with lipopolysaccharide (LPS) from Gram-negative bacteria, a potent B cell activator. To determine whether nephritis was exacerbated, we performed immunopathologic studies and tests of renal function. To verify whether nephritis exacerbation involved impairment of MPS function, we probed the kinetics of immune complex removal from the circulation, their uptake by the liver and spleen, and their localization in kidney tissue. The results indicate that in MRL mice: (i) spontaneous PBA can be enhanced by LPS; (ii) enhancement of PBA by LPS exacerbates nephritis; and (iii) the MPS is already saturated, presumably due to excessive production of endogenous immune complexes. Thus, further increase in immune complex formation due to enhanced PBA by LPS results in increased localization of immune complexes in kidneys and exacerbated nephritis.

Animals↗
PubMed1990

Mechanism of localization of immune complexes in NZB/W mice with early nephritis.

We investigated the pathogenesis of mesangial proliferative lupus nephritis in NZB/W mice under conditions that allowed us to examine removal of immune complexes from the circulation, uptake by the mononuclear phagocyte system, and localization in kidney tissue. These studies were performed at a time when variables such as the quantity of endogenous immune complexes, complement concentration, and carrier state of blood cells (platelets) were controlled. NZB/W mice and C57BL/6 (control) mice showed comparable kinetics for removal of a subsaturating dose of immune complexes (2.5 mg bovine serum albumin-antibovine serum albumin) from the circulation; additionally, the liver uptake and kidney localization of these immune complexes were comparable between NZB/W and control mice. The localization of immune complexes in the glomerular mesangium of NZB/W mice could not be attributed to enhanced production of endogenous immune complexes, to decreased removal of immune complexes from the circulation, to impaired uptake by the liver, or to complement concentration and carrier state of blood cells. It appears, by exclusion, that mesangial deposits of immunoreactants in early lupus nephritis may result from interaction of antibodies with antigens in mesangia.

Animals↗
PubMed1990

Bacterial lipopolysaccharide transforms mesangial into proliferative lupus nephritis without interfering with processing of pathogenic immune complexes in NZB/W mice.

Systemic lupus erythematosus is a multifactorial systemic disease in which genetic, immunologic, hormonal, and environmental factors may contribute to disease pathogenesis. Bacterial products (eg, bacterial lipopolysaccharide [LPS]) induce a lupuslike disease in normal mice and trigger an early and accelerated form of lupus nephritis in NZB/W mice. To investigate whether the mechanism by which LPS accelerates nephritis in the NZB/W mice involves interference with processing of immune complexes (IC), we administered LPS to NZB/W mice for 5 weeks and probed the kinetics of removal, liver uptake, and organ localization of a subsaturating dose of radiolabeled IC (2.5 mg of bovine serum albumin-antibovine serum albumin). Control NZB/W mice received vehicle (saline) alone. In NZB/W exposed to LPS, features of polyclonal B-cell activation (PBA) were enhanced, anti-DNA antibodies were raised, and a proliferative glomerulonephritis developed that was associated with renal insufficiency and substantial proteinuria. This LPS-accelerated nephritis could not be attributed to altered complement concentration, to altered blood cell carrier function, to delayed removal of pathogenic (large-sized) ICs from the circulation, to impaired liver uptake of ICs, or to enhanced localization of ICs in kidney. The findings indicate that transformation of nephritis is probably the result of LPS-induced PBA, that defective processing of pathogenic IC is not a contributory factor to nephritis, and that mechanisms other than passive renal localization of circulating ICs must be operative.

Animals↗
PubMed1989

Defective disposal of immune complexes and polyclonal B cell activation persist long after exposure to bacterial lipopolysaccharide in mice.

Patients with systemic lupus erythematosus experience clinical exacerbation during superimposed bacterial infection. Previous studies in mice indicated that heightened immune phenomena during exposure to bacterial lipopolysaccharide (LPS) appear to be related, in part, to polyclonal B cell activation, to abnormal disposal of immune complexes (IC), and to increased localization of IC in tissues. To investigate whether such effects were reversible, we administered bacterial LPS to C57BL/6 mice for 5 weeks. Control mice received vehicle alone. We then discontinued LPS, and 6 weeks later LPS and control mice were challenged with a subsaturating dose of radiolabeled IC; the removal of IC from the circulation, their localization in the liver, spleen, and kidney were determined. In comparison to values in control mice, in mice previously exposed to LPS, serologic features of polyclonal B cell activation persisted; liver uptake of pathogenic IC (greater than Ag2Ab2) was normal, but removal of small size IC (less than or equal to Ag2Ab2) from the circulation was delayed; localization of IC in the kidneys was enhanced, and pathologic proteinuria developed. The effects of repeated exposure to bacterial LPS are partially reversible, but they last long after LPS is discontinued and may contribute to altered disposal of IC, enhanced organ localization of IC, and organ dysfunction.

Animals↗
PubMed1988

Rabbit model of disseminated syphilis: immunoblot and immunohistologic evidence for a role of specific immune complexes in lesion pathogenesis.

Circulating immune complexes (CIC) containing Treponema pallidum proteins have been preliminarily implicated as inducers of a neutrophilic vascular reaction in early human cutaneous lesions of secondary syphilis. To clarify the role of specific CIC in producing cutaneous and renal lesions, 12 rabbits were studied at the following intervals after induction of disseminated syphilis: 20 days (4 rabbits: biopsies of normal and lesional skin for direct immunofluorescence (IMF) for (IgG, IgM, IgA, Clq, C3, C4), fibrin, and T. pallidum proteins; routine histology; and immunoblots of serum for CIC containing T. pallidum proteins); 21 days (4 rabbits: as at 20 days without IMF for T. pallidum protein); 23 days (4 rabbits: as at 20 days without IMF); 30 days (same 12 rabbits restudied with routine histology of normal and lesional skin; kidneys from 4 rabbits removed for routine, IMF, and electron microscopy (EM). Treponemal polypeptide antigen (MW-87 kd) was demonstrated in CIC from rabbits. Routine cutaneous histology showed evolution of lesions from an early neutrophilic vascular reaction to the typical lymphoplasmacytic reaction. IMF showed vessel-based immunoreactants in 3 of the 4 rabbits tested at 20 days and 1 of 4 at 21 days, and T. pallidum proteins in 3 of 4 rabbits at 20 days. Routine histology, IMF, and EM studies of glomeruli showed glomerular abnormalities, but no evidence of immune deposits containing specific T. pallidum protein. Skin and kidney studies of 4 controls were all negative. These data indicate a role for specific immune complexes in the pathogenesis of cutaneous lesions in this rabbit model.

Animals↗
PubMed1987

Anti-RNA polymerase I antibodies: potential role in the induction and progression of murine lupus nephritis.

Antibodies against RNA polymerase I were detected in plasma and kidney eluates of NZB/W mice. Plasma concentrations of the antibodies were the highest in mice with incipient nephritis and the lowest in mice with progressive nephritis. Mice with attenuated nephritis due to immunosuppressive therapy had intermediate plasma concentrations of the antibodies. The specific concentrations (ng/microgram IgG) of anti-RNA polymerase I antibodies in kidney eluates were significantly (10- to 70-fold) greater than the corresponding plasma concentrations. These results indicated that the decreased plasma concentration of the antibodies in mice with more advanced disease was at least partially due to selective concentration of anti-RNA polymerase I antibodies in the kidneys. The degree of this selective concentration was directly proportional (R2 = 0.9962) to the severity of renal disease, as reflected by the concentration (microgram/g tissue) of IgG eluted from the kidneys. The concentration (microgram/g tissue) of anti-RNA polymerase I eluted from the kidneys also was increased in mice with more severe renal disease. Further, the extent of this increase was greater than that of total IgG, again suggesting that anti-RNA polymerase I antibodies had been selectively concentrated in the kidneys. These findings are strongly suggestive of an important role for the RNA polymerase I/anti-RNA polymerase I antibody system in the pathogenesis of murine lupus nephritis.

Animals↗
PubMed1987

Familial adult glomerulocystic kidney disease.

During an evaluation for nephrotic syndrome, a 20-year-old woman was found by ultrasonographic examination to have large kidneys with multiple renal cysts suggestive of polycystic kidney disease. A subsequent renal biopsy revealed membranous glomerulopathy due to systemic lupus erythematosus, as well as the unexpected finding of glomerulocystic kidney disease (GCKD), an uncommon disorder previously reported to occur primarily in infants and children. No evidence of renal dysplasia was present and no cysts were found in any abdominal or pelvic organs. Other than one bifid renal pelvis, no significant congenital anomalies or structural chromosomal abnormalities were present. Ultrasonographic evaluation of the patient's family revealed similar-appearing cortical cysts in several members, all of whom had no clinical evidence of renal dysfunction. The pattern of involvement was compatible with autosomal dominant inheritance. Follow-up ultrasonograms of the patient and affected family members 1 year after the initial study showed enlargement of the cysts with development of additional cysts in two individuals and no change in the other family members. Although renal failure was present and progressed in our patient, renal function remained normal in all affected family members 1 year after detection of the renal cysts. This patient and her family provide additional insight into the inheritance and natural history of GCKD and demonstrate that this condition should be considered in the evaluation of multicystic renal disease in adults. In contrast to several previously reported cases, it appears that GCKD may be associated with normal renal function for many years.

Adolescent↗