Biomedical subjects
Publications and source records attributed to H Helin.
IgA nephropathy was found in three patients with celiac disease; two of them also had dermatitis herpetiformis. These observed associations widen the spectrum of the diseases that have been reported to coexist with IgA nephropathy. This study focused on the possible intestinal origin of the glomerulonephritis.
A 34 year old woman is described in whom carditis, arthritis, fever, leukocytosis and a high sedimentation rate developed two weeks after a streptococcal infection. The patient also had the nephrotic syndrome and rapidly progressive renal insufficiency. The renal biopsy specimen showed acute extracapillary (crescentic) glomerulonephritis. The initial response to corticosteroid therapy was good, but later a slowly progressive renal function impairment was seen.
In a series of 374 renal biopsy specimens, 26 from patients with primary glomerulonephritis showed IgM as the main glomerular immunofluorescence finding. By light microscopy 17 of these specimens showed mild mesangial hypercellularity and 9 were normal. Small mesangial electron-dense deposits were seen in 8 specimens. Of the 26 patients, 10 had proteinuria, 6 had the nephrotic syndrome, 6 had hematuria and 4 had both proteinuria and hematuria. The mean serum IgM level was significantly higher in the patients than in healthy controls. Circulating immune complexes were detected by three methods in 39% of the patients.
A study was undertaken to evaluate some processing variables affecting the immunoelectron microscopic demonstration of immunoglobulins and complement (C3) in human glomeruli. Percutaneous biopsies were performed on 28 patients with various types of glomerulonephritis. Light microscopic, electron microscopic, and immunofluorescence examinations were performed by routine methods. For immunoelectron microscopy, fixation in paraformaldehyde (PA) or periodate-lysine-paraformaldehyde (PLP) was used. With the diffusion technique, using tissue chopper or cryostat sections, human immunoglobulin (Ig)G, IgA, IgM, and C3 were localized in glomeruli with peroxidase-labeled antisera. Using PLP and the tissue chopper sections, good ultrastructure was achieved. The antigens could be demonstrated in intramembranous, subepithelial, subendothelial, or mesangial immune deposits. Penetration of antibodies and quality of peroxidase reaction in the cryostat sections did not differ from that of the tissue chopper sections. Freezing and thawing, however, resulted in inferior morphology. If PA was used, the antigens could not be reliably demonstrated. The results of light microscopy, electron microscopy, and immunofluorescence microscopy were in good agreement with those from the immunoperoxidase procedure. The present study shows that PLP preserves well the antigenicity of human immunoglobulins and C3, resulting in good ultrastructure. PA fixation, on the contrary, caused a loss of antigenicity before an adequate ultrastructure could be achieved.
Avidin, a specific progesterone inducible protein, was localized in the oviduct magnum mucosa of chicks treated with diethylstilbestrol (DES) or DES plus progesterone, using ultrastructural immunoperoxidase techniques. Diffusion technique and the double or triple layer peroxidase staining method were applied. The results obtained by immunoelectron microscopic peroxidase techniques with high resolution power indicated that progesterone stimulation in the DES-treated chicks resulted in avidin production in the goblet cells of the oviduct epithelium. The sensitive-antiperoxidase staining method revealed a slight avidin production in many goblet cells of chicks treated with only DES. This method also showed some avidin-positive ciliated epithelial cells in chicks treated with progesterone. This results suggest that some ciliated epithelial cells may have functional or metabolic properties characteristic of secretory goblet cells.
Four patients suffering from protracted dermatitis herpetiformis (DH) developed lymphomas while undergoing gluten-free diet treatment. This had lasted between 6 months and 4 years. The first patient died of histiocytic lymphoma involving mesenterial lymph nodes, liver, spleen and blood marrow. The second patient died of histiocytic lymphoma disseminated in the ileum, colon, stomach and mesenterium. This patient had been operated on 14 years earlier for a solitary ulcerating lymphoma in the ileum. The third patient had a localized histiocytic lymphoma in the colon. This was successfully removed by hemicholectomy. The fourth patient had a lymphocytic lymphoma of B-cell origin in the inguinal lymph nodes which was treated with radiotherapy. These 4 patients with lymphomas suggest that, like coeliac disease patients, DH patients also run an increased risk of developing lymphomas.
Pancreatic vessel wall alterations were studied in tissue material obtained from six patients subjected to resection of the gland for acute necrotizing pancreatitis. Special attention was paid to elastic tissue damage, which was studied using special stains in light and electron microscopy. Vascular wall elastic laminae showed changes varying from fragmentation to complete dissolution. The outer elastic lamina was more consistently affected. Elastic tissue damage was observed in pancreatic areas with minor acinar alterations and in vessels with otherwise relatively well-preserved walls. These observations suggest 1/ an early participation of elastase in the production of tissue damage in human acute pancreatitis and 2/ a primary role for elastic tissue injury in the vascular alterations leading to haemorrhage and tissue necrosis through ischaemia.
Two cases of patients with a bronchial small-cell carcinoma coexisting with IgA nephropathy are reported. The relationship of the bronchial malignancy to IgA nephropathy is discussed.
Eleven patients with amyloidosis were treated for terminal renal failure by transplantation, receiving 12 cadaver allografts. In one patient the amyloidosis was primary and in the remaining 10 it was secondary to a chronic inflammatory disease. All of the patients were subjected to one or two fine-needle aspiration biopsies of the kidney graft during a followup of 11 to 68 months. The biopsies of three patients, one with primary amyloidosis and two with ankylosing spondylitis, revealed amyloid recurrence in the graft. These recurrences were diagnosed at 11, 28, or 37 months, respectively. The risk of amyloid recurrence is thus by no means negligible. The present study revealed no factors determining the development of recurrence. In two additional cases, membranous glomerulonephritis was observed in transplant biopsy. Both of these patients had rheumatoid arthritis as the underlying disease and were treated with gold salts before transplantation. It is suggested that an impaired immune response, related to amyloidosis and/or immunosuppressive therapy, may have favored the formation and deposition of circulating immune complexes.
A series of 40 IgA nephropathy patients is presented. IgA nephropathy was the most common (24%) type of glomerulonephritis in our renal biopsy material. Circulating immune complexes were measured by five methods that gave a positive result in 9-69% of the patients. The platelet aggregation test with heated serum (PAT2) was by far the most commonly positive. The serum concentrations of IgA were measured by two methods, radial immunodiffusion and laser nephelometry. Both tests gave similar results. 58% of the patients had elevated serum IgA. There was no statistically significant association between HLA antigens and IgA nephropathy as compared with the control material.
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Ultrastructural alterations in pancreatic acini from six patients operated for acute necrotizing pancreatitis are described. One of the patients suffered from biliary tract disease, the rest had excessive alcohol intake as the presumed aetiology. Areas of the pancreatic parenchyma showing oedematous inflammation in light microscopy were studied in the electron microscope. Findings in acinar cells included changes in zymogen granules and an increased autophagocytosis in addition to unspecific organelle alterations. Zymogen granules showed increase in size and number, loss or variation of electron-density and peripheral dissolution. Increased autophagic activity was indicated by several autophagic vacuoles and residual bodies. Acinar lumina were dilated showing effacement of microvilli and invaginations in the luminal plasma membrane of the acinar cells. In acinar lumina and in the interstitium fibrillar material was observed, with an increasing frequency in those areas showing severe cellular disintegration. These findings suggest: 1) an increased activity of zymogen granules, 2) an increased autophagocytosis, and 3) penetration of acinar luminal contents into the interstitium.
Fixation and embedding variables were compared in immuno-electron microscopic localization of rat IgG in an autologous immune complex-type nephritis. Specimens from kidney cortex were fixed for 3, 6 or 9 h in the following fixatives made in 0.1 M phosphate buffer at pH 7.4: 4% paraformaldehyde, 2.5% glutaraldehyde, periodate- lysine-paraformaldehyde or modified Karnovsky's fixative. Localization of IgG was performed on tissue sections cut with a tissue chopper, cryostat or sliding microtome, using agarose, Ames O.C.T. Compound or polyethylene glycol respectively as cutting matrixes. The sections were incubated in peroxidase-labelled antirat IgG antiserum (diluted 1:20 with phosphate-buffered saline) for 60 h. Peroxidase activity was then revealed and the sections embedded in Epon. Exact localization of IgG throughout the sections and good ultrastructure were achieved when paraformaldehyde and agarose were used. Periodatelysine-paraformaldehyde proved almost as useful as paraformaldehyde in connection with agarose in respect of peroxidase reaction and ultrastructure. Fixatives containing glutaraldehyde gave a mostly weak and unevenly distributed peroxidase reaction product. In the cryostat sections breaking of the tissue structure could not be avoided. When polyethylene glycol was used as cutting matrix no peroxidase reaction was achieved.
43 renal fine-needles aspirates, obtained with a modified sampling technique were subjected to ultrastructural examination with the aim of assessing the diagnostic value of this method in various glomerular diseases. Findings in the aspiration specimens, consisting of solitary glomeruli, were regarded as diagnostic in 35% of the cases. When considered together with clinical data, the fine-needle aspiration biopsies were suggestive of diagnosis or provided valuable information in a further 49% of the cases. Due to the small outer diameter of the fine-needle, 0.7 mm, complications following this kind of biopsy are practically negligible. Thus, it offers a safe alternative to the conventional renal biopsy methods utilizing large-bored cutting needles in cases where biopsies with these methods are contraindicated.
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39 patients with malignant neoplasms were studied for the presence of paraneoplastic glomerular disease. The nephrotic syndrome was found in none of the patients. From 24 patients an adequate renal biopsy specimen was available for examination by electron microscopy. Glomerular electron-dense deposits were found in the biopsies of 11 patients, and in four of them the deposits were subepithelial. Circulating soluble immune complexes were detected in the sera of 14 patients. Deposits and circulating immune complexes occurred simultaneously with a highly significant correlation. Cell-mediated immunity was studied using skin tests to tuberculin and dinitrochlorobenzene (DNCB). Negative tests were seen mainly in patients with circulating immune complexes and/or glomerular deposits. Median survival time in patients with deposits or circulating complexes tended to be shorter than in those without.
Experimental glomerulonephritis was produced in 16 rabbits by intravenous injections of ovalbumin in high doses (0.1 g/day during the first week, 0.2 g x 6/day during the second). The animals were killed on day 14. At that time all animals had 2--4+ proteinuria and a serum C3 level reduced to about 50% of the control level; 11 animals had a significantly raised blood urea level. In all rabbits the antigen had induced severe proliferative glomerulonephritis. Electron microscopy showed that many of the cells accounting for the hypercellularity were monocytes. Surprisingly, electron dense deposits were few and small, mainly on the subendothelial and subepithelial aspects of the glomerular basement membrane. In all the animals ultrastructural immunoperoxidase technique revealed deposits containing ovalbumin, rabbit IgG and C3. With immunofluorescence sparse deposits were occasionally seen. It is concluded that a severe experimental glomerulonephritis can be produced in a state of antigen excess, with the deposition of immune complexes being minimal. Immuno-electron microscopy is essential, however, in detecting even the smallest animals of deposited immune reactants.
Lymph node and peripheral blood lymphocytes in a case of Hodgkin's disease (mixed cellularity) were studied using May-Grünwald-Giemsa (MGG), acid naphthyl acetate esterase (ANAE), immunoperoxidase staining and lymphocyte surface markers, autoradiographic, and lymphocyte stimulation techniques. According to MGG staining and autoradiographic studies of lymph, node cells, small lymphocytes, intermediate lymphoid cells, and large mononuclear cells resembling in-vitro stimulated immunoblasts, Hodgkin's cells and Reed-Sternberg (RS) cells formed a morphologically continuous DNA synthetizing series. A large majority of small lymphocytes from a lymph node were ANAE positive, thus being T-lymphocytes, and formed rosetts around large mononuclear cells and RS cells. Most RS and large mononuclear cells had ANAE positive spots in the cytoplasm, thus resembling T-lymphocytes more than diffusely staining monocytes. These cells did not contain cytoplasmic immunoglobulin and were muramidase negative. Both lymph node and peripheral blood lymphocytes responded strongly to PHA. The role of T-lymphocytes in Hodgkin's disease and the origin of RS cells are are discussed on the basis of the findings.