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T Törnroth

Publications and source records attributed to T Törnroth.

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

Binding of bacterial adhesins to rat glomerular mesangium in vivo.

Two well characterized bacterial adhesins, the O75X fimbriae of Escherichia coli and the type-3 fimbriae of Klebsiellae, with in vitro affinities to type IV and V collagens, respectively, were used to test whether bacterial components with affinity for glomerular matrix could bind to glomeruli in vivo. The purified fimbrial proteins were injected into rats, and kidney samples were studied by immunofluorescence at two hours to nine months postinjection. The O75X, but not the type-3 fimbriae, formed mesangial deposits that persisted for months. Preincubation of the O75X fimbriae with type IV collagen significantly reduced the glomerular binding. The fimbrial deposits were extracellular, as anti-O75X IgG injected into rats bound to glomeruli. Proteinuria or histological damage could not be detected even after passive or active immunizations of the rats. The results demonstrate that bacterial adhesins may bind in vivo to and persist in glomeruli by their specific affinities. The results also indicate that additional factors provided by the bacteria or the host are needed for glomerular damage to take place.

Adhesins, Bacterial↗
PubMed1992

Activation of the alternative pathway of complement by monoclonal lambda light chains in membranoproliferative glomerulonephritis.

Immunopathological evidence suggests that activation of the alternative pathway of complement (AP) is involved in membranoproliferative glomerulonephritis (MPGN) and in immunoglobulin A nephropathy. In this report we describe an AP dysfunction-associated factor that was isolated from the serum and urine of a patient with hypocomplementemic MPGN. Extensive glomerular deposits of C3, properdin, and of the terminal complement components were observed in the kidney of the patient. In her serum the AP hemolytic activity was virtually absent. When mixed with fresh normal serum, the patient's serum induced a 96% C3 conversion during a 30-min incubation at +37 degrees C. This activity was found to be due to a circulating factor that by immunochemical characterization proved to be a 46-kD monoclonal immunoglobulin lambda light (L) chain dimer (lambda L). Purified lambda L, but not control lambda or kappa L chains from patients with L chain disease, activated the AP in a dose- and ionic strength-dependent manner. Functionally, lambda L was differentiated from C3 nephritic factor (an autoantibody against the AP C3 convertase, C3bBb) by its inability to bind to and stabilize the C3bBb enzyme. Instead, lambda L was observed to interact directly with the AP control factor H. Thus, lambda L represents a novel type of immunoglobulin-related AP-activating factor with the capacity to initiate alternative complement pathway activation in the fluid phase.

Antibodies, Monoclonal↗
PubMed1990

The effect of cyclosporin A on the interstitial mononuclear cell infiltration and the induction of Heymann's nephritis.

Heymann's nephritis was induced with brush-border (BB) antigen. Interstitial mononuclear cell infiltration was studied with cytological examinations of fine-needle aspiration biopsies (FNAB), and with immunoperoxidase stains of frozen sections with monoclonal antisera. The effect of cyclosporin A (CyA), 20 mg/kg when administered intraperitoneally for 8 days in association with both initial immunization, and with the booster 4 weeks later, on the interstitial leukocyte infiltration and on the development of membranous glomerulonephritis (MGN) and proteinuria were investigated. Another group of rats was immunized, but not given CyA. Experimental animals were killed in groups 3, 6 and 20 weeks after initial immunization. CyA inhibited significantly the initial interstitial lymphocyte and blast cell response at 3 weeks (FNAB), but did not inhibit the secondary response after the booster. The anti-BB titre reacted in a similar fashion. Immunoperoxidase stains indicated a clearly suppressed T suppressor/cytolytic (T s/c) cell response. Glomerular basement membrane (GBM) deposits of IgG developed more slowly and were more scarce in the CyA-treated rats, when compared with the untreated group. Only one out of 15 CyA treated rats developed C3 deposits in the GBM during the course of the study, and none developed proteinuria, when most untreated rats (10/17) had C3 deposits and were nephrotic at 20 weeks. Thus, CyA depressed the initial interstitial cellular response after immunization with BB antigen, and also inhibited the development of antibody response, C3 deposits and proteinuria of Heymann nephritis. These effects of CyA may be contributed to an inhibited amplification of the autoimmune response associated with interstitial damage and continuous release of autoantigen.

Animals↗
PubMed1990

Abnormally thin glomerular basement membrane and the Goodpasture epitope.

Using indirect immunofluorescence, cryostat sections from renal biopsy specimens of 14 adult patients showing marked diffuse thinning of the glomerular basement membrane (GBM) on ultrastructural analysis were examined for the presence of the Goodpasture (GP) epitope M2 using anti-M2 antiserum. In no case was a total absence of M2 noted. The fluorescence pattern was fine but homogeneously linear along the GBM in 12 cases, intensity varying from +-++, as compared with for the control specimen GBM. A faint, broken line of stain, intensity+, was observed in biopsy specimens of two patients, one of whom had family members with progressive hereditary nephritis, type Alport's syndrome. Clinical presentation was dominated by hematuria (10/14 patients) but also included three patients with isolated proteinuria. Two patients had nephrotic range proteinuria. Other than the GBM changes, histological findings were sparse, with either no abnormalities or only slight mesangial increase in most. One case of focal segmental sclerosis and hyalinosis was also found. The findings from this study suggest that the abnormally thin GBM does not lack the GP epitope, but it may be reduced.

Adult↗
PubMed1990

Interstitial cellular infiltration detected by fine-needle aspiration biopsy in nephritis.

Fine-needle aspiration biopsy (FNAB) was used to detect renal mononuclear interstitial inflammation in 56 patients with various types of nephritis (20 IgA nephropathy, 8 focal necrotizing glomerulonephritis, 7 interstitial nephritis, 6 non-classifiable chronic glomerulonephritis, 5 mesangial proliferative (non-IgA) chronic glomerulonephritis, 4 focal glomerulosclerosis, 6 normal histology, who were examined for microscopic hematuria, and 7 controls). Regular renal biopsies for histological and immunofluorescence studies were simultaneously obtained, and available for comparative analysis (not controls). Differential counts of mononuclear infiltration and subtyping of T-cell infiltration into T-helper (T-h) and T-suppressor-cytotoxic (T-s-c) cells, as detected by immunoperoxidase stains from FNAB, were correlated to clinical manifestations and renal function tests. Generally, our results indicated increased mononuclear cell infiltration (monocytes, lymphocytes, and/or activated lymphocytes) in FNAB of patients with IgA nephropathy, interstitial nephritis or focal necrotizing glomerulonephritis (especially monocytes in IgA nephropathy and interstitial nephritis, p less than 0.05 compared with controls, lymphocytes in focal necrotizing glomerulonephritis, and non-classifiable glomerulonephritis, p less than 0.02 and 0.05, respectively). The number of infiltrating activated lymphocytes was significantly increased in focal necrotizing glomerulonephritis, interstitial nephritis and focal glomerulosclerosis, p less than 0.05, less than 0.01 and less than 0.01, respectively. FNAB was at least as sensitive as histological examination for the quantification of interstitial cellular infiltration, and it allowed for cytological differential counts. Patients had decreased T-h and increased T-s-c cell counts, which were accentuated in FNAB compared with peripheral blood, although there were strong positive correlations between local and peripheral counts (p less than 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Preparative polyacrylamide gel electrophoresis in the isolation of the nephritogenic proteins of passive Heymann nephritis.

To study kidney antigens involved in the formation of glomerular subepithelial immune deposits in passive Heymann nephritis polypeptides of 500, 130 and 105 kDa were isolated from rat kidney brush border (BB) membrane fraction using preparative polyacrylamide gel electrophoresis. Polyclonal antibodies raised against these proteins were specific for their respective antigens in immunoblotting. All three antisera bound to proximal tubular BB of kidney and to apical surfaces of several other epithelia as shown by indirect immunofluorescence on frozen sections of normal rat tissues. The anti-500 kDa and anti-105 kDa, but not the anti-130 kDa, antibodies also stained glomeruli and the anti-105 kDa antibodies also endothelial cells. After injection into rats the anti-500 kDa IgG bound to kidney glomeruli forming diffuse, granular deposits of rabbit IgG along the glomerular capillary walls, as shown by direct immunofluorescence. In electron microscopy the immune deposits were subepithelial and electron dense. The deposits remained in glomeruli for at least 60 days and increased with time. Deposits of C3 were not detected and proteinuria did not develop. The anti-130 kDa and the anti-105 kDa IgGs did not form glomerular deposits after in vivo injections. The results suggest that the 500 kDa and the 105 kDa proteins or related antigens are present in glomeruli and the 500 kDa protein is located on the epithelial side of the glomerular basement membrane. Circulating antibodies can bind to the 500 kDa protein forming immune complexes which rearrange and form electron dense deposits. The results further demonstrate that preparative gel electrophoresis is a useful technique for the isolation of kidney proteins of immunopathologic interest.

Animals↗
PubMed1987

The evolution of membranous glomerulonephritis reconsidered: new insights from a study on relapsing disease.

Membranous glomerulonephritis (MGN) has a highly variable clinical course. The morphological basis for this variability has not been fully elucidated. We studied 10 patients with relapsing MGN and compared the findings with those in other clinical courses. The mean duration of follow-up was 10.4 years. Clinical remission occurred, on average, 1.5 years and relapse, on average, 5.6 years after onset. Thirty-one renal biopsies obtained at various clinical phases were studied, 22 of them electron microscopically. The ultrastructural and clinical alterations paralleled each other closely. Subepithelial electron-dense deposits were present during the primary nephrotic phase, were replaced by intramembranous lucent deposits during remission, and reappeared again during relapse. Light microscopic changes (projections, thickening) of the glomerular capillary basement membrane (GBM) were variable. Both ultrastructural and light microscopic changes were unreliable indicators of the duration of illness. A comparative analysis of the present and previous findings suggests that the length of time during which new deposit material is formed determines the evolution of the membranous lesion and the corresponding clinical course. Thus, a short duration results in a single generation of deposits, a morphologically and clinically healing course, and no thickening of the GBM. A repeated formation of deposit material results in a new generation of subepithelial deposits, and a relapsing course. A prolonged formation results in a continuous presence of subepithelial deposits, a thickening of the GBM, and a protracted or progressive course. The morphologic staging currently in use pertains to one particular evolution and course of MGN and therefore should not be used.

Adult↗
PubMed1987

Recurrent and de novo glomerulonephritis in allografted kidneys: aspects of ultrastructural diagnosis.

Allograft glomerulonephritis (GN) is a noteworthy alternative in the differential diagnosis of renal graft dysfunction. The true frequency of allograft GN is unknown; a rough estimate is 5-15%. The highest rates of recurrence (100-20%) have been reported, in decreasing order of frequency, in mesangiocapillary GN (MCGN) type 2, IgA nephropathy, MCGN type 1, and focal segmental glomerulosclerosis (FSGS). In addition, in about 2% of allografts membranous GN (MGN) occurs as a de novo lesion. Electron microscopy has proved valuable in detecting early or mild MGN, MCGN type 2 and FSGS, and in differentiating between MCGN type 1 and allograft (rejection) glomerulopathy. Even with the aid of electron microscopy, however, the demarcation between MCGN type 1 and allograft glomerulopathy may prove impossible. The finding of prominent mesangial deposits (in an otherwise normal allograft), is highly suggestive of recurrent IgA nephropathy.

Glomerulonephritis↗
PubMed1987

Interstitial mononuclear cell infiltration in Heymann nephritis.

Interstitial mononuclear cell infiltration in rats during the development of autoimmune Heymann nephritis (HN) was studied using the fine-needle aspiration biopsy (FNAB) technique. The results were compared with those obtained by immunohistochemical studies of infiltrating T helper (T-h) and T suppressor/cytotoxic (T-s) cells, and with traditional histopathological and immunofluorescence examinations. Three weeks after initial immunization with isolated tubular brush border antigen, when the histopathological finding was quite normal, FNAB revealed increased numbers of interstitial blast cells, large granular lymphocytes and activated lymphocytes. These increases reached significant levels 2 weeks after a booster injection and were still prominent in a few rats with manifest membranous glomerulonephritis (MGN) and proteinuria 14 weeks after initial immunization. Immunohistochemical staining 3 weeks after immunization showed a significant increase in T-h cells in peritubular regions. Infiltration decreased successively 2 weeks after the booster and during manifest MGN. On the other hand, the mean number of cortically infiltrating T-s cells successively increased during the course of the study and this increase had reached a statistically significant level 2 weeks after the booster. Prominent T-s infiltration appeared in a few rats 2 weeks after the booster and when MGN was histopathologically manifest, and it was then associated with histopathologically detectable interstitial mononuclear infiltration and also with blast cell infiltration in FNAB. Our results suggest linkage between tubulointerstitial lesions in HN and cell-mediated immunoreactivity, and that severe interstitial inflammation is associated with T-s cell infiltration. Cytological interpretation indicated that infiltrating blast cells were plasmablasts, which may imply local antibody production, especially since anti-brush border antibody titres and blast cell infiltration simultaneously reached maximum levels 2 weeks after the booster.

Animals↗
PubMed1987

Renal mononuclear inflammatory cell populations in membranous glomerulonephritis: a fine-needle aspiration biopsy study.

Fine-needle aspiration biopsy (FNAB) technique was applied to the detection of alterations in renal inflammatory cell subsets in seven healthy control persons and 24 patients with membranous glomerulonephritis (MGN). Eighteen of the patients had nephrotic syndrome, and the rest had either persistent proteinuria or remission of the disease. Only one patient showed impaired renal function. Compared with the controls, FNAB revealed a significantly (p less than 0.01) increased number of mononuclear inflammatory cells (MIC, the sum in increment percentages of lymphocytes and monocytes) in MGN. This was mainly due to relative lymphocytosis; the number of monocytes was high particularly in patients with daily urine protein excretion in excess of 5 g. The duration of the disease did not clearly correlate with the degree of lympho- or monocytosis. In nine patients the results of the renal needle biopsy and FNAB could be compared. Biopsy revealed signs of MIC infiltration in 5/9 patients and FNAB in 7/9 patients. T-lymphocyte subsets in FNAB and peripheral blood were analyzed using monoclonal antibodies and indirect immunoperoxidase technique. The OKT4/OKT8 ratio in FNAB was 0.96 +/- 0.07 (s.e.m.) in patients and 1.49 +/- 0.12 in controls (p less than 0.01). In peripheral blood these ratios were 0.8 +/- 0.07 and 1.43 +/- 0.13 (p less than 0.001), respectively. The alterations were due to a decreased number of OKT4 positive lymphocytes. These studies suggest an associated interstitial accumulation of MIC and an imbalance between T helper/inducer and T suppressor/cytotoxic cells in MGN.

Adult↗
PubMed1987

AA amyloidosis in systemic lupus erythematosus.

A 37-year-old woman with longstanding systemic lupus erythematosus developed cardiac insufficiency, nephrotic syndrome, and azotemia. The findings at echocardiography and cardiac scintigraphy suggested amyloidosis, which was confirmed by rectal biopsy and fine needle biopsy of subcutaneous abdominal fat. Postmortem examination revealed systemic amyloidosis with massive deposits in the heart, spleen and kidneys. She had persistently increased concentration of serum amyloid A protein during the last 4 years of her life, and her amyloidosis was of the secondary (AA) type, as shown by immunohistochemical studies.

Adult↗
PubMed1987

Membranous glomerulonephritis in rheumatoid arthritis not related to gold or D-penicillamine therapy: a report of four cases and review of the literature.

In a series of 96 patients with membranous glomerulonephritis (MGN) there were 14 who had concomitant rheumatoid arthritis. Ten of these had been treated with gold or D-penicillamine; in four patients neither of these drugs could have been responsible for the MGN. One of them received intrasynovial osmium tetroxide two months before the clinical onset of MGN. Three of the patients had positive rheumatoid factor. HLA-type was examined in three patients and all showed B27 antigen but not DR3. No patient developed signs of systemic lupus erythematosus during the follow-up (mean 5.9 years). In two patients MGN persisted as judged from urinary abnormalities, one patient recovered after a relapse period and one developed secondary amyloidosis.

Adult↗
PubMed1986

Reversible non-oliguric impairment of renal function during azapropazone treatment.

An impairment of the renal function was observed in three patients who received azapropazone for various rheumatic disorders with simultaneous hyperuricaemia. A distinct increase in serum creatinine occurred in all patients. In one case the renal biopsy suggested a hypersensitivity reaction with a consequent acute tubulo-interstitial nephritis as the mechanism of the impaired renal function. The renal insufficiency was reversible in all cases after the withdrawal of azapropazone.

Acute Disease↗