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Biomedical subjects

J Ormos

Publications and source records attributed to J Ormos.

At least 19 recordsLinked to original sources

[Simultaneous occurrence of persistent hematuria (thin basement membrane nephropathy) and light-chain proteinuria (benign monoclonal gammopathy) in a middle-aged male].

IgG lambda type of monoclonal gammopathy and thin basement membrane nephropathy were established in a middle-aged man examined because of persistent haematuria, lambda light-chain proteinuria and moderately diminished renal function. A 10% level of plasmocytosis was verified by bone-marrow aspiration. The more than 6-year follow-up showed the gammopathy to be benign. The thin basement membrane nephropathy was verified by electronmicroscopic analysis of renal tissue obtained by percutaneous renal biopsy: lamina densa of the glomerular capillaries thinned to 30-100 nm. In spite of the usually good outcome of thin basement membrane nephropathy, in this case it was accompanied by glomerular sclerosis, subsequent destruction of nephrons, hypertensive vascular alterations and a clinical deterioration of the renal function after 4 years. A rebiopsy excluded the possible complications (amyloidosis, non-amyloid immunoglobulin nephropathy, cylinder nephropathy, etc) of light-chain proteinuria.

Adult

Hereditary nephritis, platelet disorders and deafness-Epstein's syndrome.

A 14-year-old boy with persistent proteinuria (1.6-4.0 g/day), microscopic haematuria, moderate hypertension, macrothrombocytopenia (giant platelets, platelet number 30 x 10(9)/l) and a familial sensorineural hearing loss (the father and the brother were also affected) was studied. Kidney biopsy revealed a diffuse mesangial proliferation, and a focal thickening of the glomerular basement membrane was seen on electron microscopy. A normal number of megakaryocytes was observed in bone marrow aspirates. The aggregation response of the platelets to collagen, epinephrine and adenosine diphosphate (ADP) was decreased. The platelet number was slightly diminished, platelets were of normal size in both parents and the brother, and showed a decreased aggregability in response to collagen, epinephrine and ADP in the brother and mother. No functional abnormality of the platelets was observed in the father. Urinalysis and kidney function were normal in the family members. This boy with nephritis, platelet disorders and hearing loss corresponds to Epstein's syndrome.

Adolescent

[Secondary membranous glomerulonephritis].

Following 689 percutaneous renal biopsies, membranous glomerulonephritis was proved in 68 patients. In 16 (23.5%) an underlying primary disease was verified, and thus the glomerulonephritis the secondary form. The primary disease was SLE in 5 cases, diabetes mellitus in 5 cases, rheumatoid arthritis in 3 cases, chronic active hepatitis in 2 cases, an ulcerative colitis and eosinophilic angiolymphoid hyperplasia in 1 patient. As initial sign, nephrotic syndrome emerged in 87.5% of the 16 cases. Microscopic haematuria was observed in half of the patients, as was hypertension, while acute renal failure presented in only 1 case. Histologically, in 13 cases the predominance of early glomerular alterations was characteristic, while in 9 cases the picture proved to be equivocal and accompanied by some degree of interstitial alterations. During combined treatment, remission was achieved in 75%. Two patients with SLE died, but not as a consequence of renal failure. Transient side-effects of the treatment were registered in 5 cases. The principal pathogenetic and clinical differences between the individual secondary nephritis forms, and the difficulty of their differentiation from the idiopathic cases, even on repeated examination, are emphasized. In 3 patients the possibility of secondary renal processes was suggested by the histological picture, and this was proved by the detailed clinical findings.

Adult

Importance of plasma cells in the infiltrate of renal allografts. An immunohistochemical study.

The cellular infiltration in 42 needle and wedge biopsies of transplanted kidneys was investigated immunohistochemically. The percentages of helper/inducer (CD 4+) cells, suppressor/cytotoxic cells (CD 8+), B lymphocytes, macrophages, plasma cells (Pc) and granulocytes were determined. The proportions of the various inflammatory cell populations were established in acute interstitial rejection (AIR), acute vascular rejection (AVR), chronic rejection (CR) and cyclosporin A nephrotoxicity (CsAN). The most prominent differences were detected as regards the Pc, whose number was much higher in CR than in AIR, AVR or CsAN. The striking difference between CR and CsAN in the number of Pc may be of differential diagnostic importance: the presence of many Pc in the biopsies can be regarded as a sign of CR. Over 80% of the Pc in CR contained IgG, whereas in chronic interstitial nephritis (CIN) the IgA-positive Pc predominated. In AIR, AVR and CsAN, too, the majority of the Pc contained IgG, but the numbers of IgM and IgA-positive cells were also relatively high. The great number of IgG-positive Pc indicates an important role of a secondary type humoral immune response in CR.

Cell Count

Adenocarcinoma of ceruminous glands. Ultrastructural, immunohistochemical and lectin histochemical studies.

A case of ceruminous adenocarcinoma is reported. The tumor destroyed the right pyramid, widely invaded the base of the skull and caused death shortly after the diagnosis. Distant metastases were not found by autopsy. The tumour cells reacted with epithelial markers and with the antibody against S-100 protein. Heparan sulphate proteoglycan seemed to be a good marker for detecting basement membrane ruptures and concomitant tumour invasion. Among the lectins BS-I and PNA gave the strongest reactions in the stroma. This is the first immunohistochemical and lectin histochemical report on ceruminous adenocarcinoma.

Adenocarcinoma

Comparative distribution of laminin and collagen types I, III and IV in transplant vasculopathy.

Composition of the extracellular matrix (ECM) was studied in transplant vasculopathy occurring in rejected renal allografts using the immunoperoxidase technique with antisera against laminin, and collagen types I, III and IV. In acute transplant vasculopathy the loose ECM network of the intima showed intense immunostaining for laminin and type IV collagen. Type III collagen was detected in the advanced acute cellular intimal proliferations, while early acute lesions did not show immunreactions. Type I collagen was not seen in significant amount. In contrast to these findings in chronic transplant vasculopathy associated with intimal fibrosis the ECM was largely composed of interstitial collagen types III and I, while staining for the basement membrane type ECM components were markedly reduced. Degradation of the matrix components with variable composition was noted in foci of mononuclear infiltrates occurring inside the fibrotic intima. These results indicate that the ECM shows a compositional change in transplant vasculopathy which is associated with the age of the lesion.

Collagen

Pathogenesis of transplantation arteriopathy. Myointimal cells express HLA-DR antigens during rejection.

Arteries were investigated ultrastructurally in material from 40 needle and wedge biopsies of renal allografts, and immunohistochemically in another 10 cases with signs of chronic obliterative transplantation arteriopathy. In the early biopsies, but even in the control kidneys, thin extensions of the smooth muscle cells of the media were observed, which were in direct contact with the endothelial cells through the lamina elastica interna. These extensions may contain receptors mediating endothelial noxae to the smooth muscle cells thus initiating their proliferation, migration to the intima presumably begins in the early post-transplant period and continues until the lumen is occluded. Concomitantly, inflammatory cells (mainly macrophages, with a smaller number of CD4 and CD8-positive T lymphocytes) invade the intima. The proliferating myointimal cells, possibly having become HLA-DR-positive, may behave as antigen-presenting cells, enhancing the anti-graft immune response further, and aggravating the arterial injury.

Cell Movement

Morphological characterization of human juxtaglomerular apparatus.

The recent demonstration of the endothelial fenestration at the juxtaglomerular part of the afferent arteriole facing mesangial and granular cells and finger-like protrusions of urinary space into the region of the lacis in experimental animals like the rat, the mouse, and Tupaia belangeri led us to propose the hypothesis of a "short loop" feedback mechanism. To establish whether a further species possesses these morphological features, the JGA region was examined in the human kidney. Tissue was obtained by needle biopsy from patients and conventional electron-microscopical procedures including serial sections were utilized to reevaluate the morphology of JGA. Both the endothelial fenestration in the wall of the afferent arteriole and protrusions with filtration slits of urinary space into the lacis, were observed with remarkable heterogeneity. The occurrence of these features of JGA in such diverse mammalian species as rat, mouse, Tupaia, and man suggests that these structures may be involved in regulatory process and the proposed "short loop" feedback mechanism may be a general phenomenon.

Animals

[Characteristics of cellular infiltration in rejected renal grafts].

The composition of the cellular infiltrate in 42 needle and wedge biopsies of transplanted kidneys was investigated immunohistochemically. The various inflammatory cell populations were examined in different rejection types and cyclosporin-A nephrotoxicity (CsAN) as well as in different locations in the graft (perivascular and intertubular area, tubular epithelium, glomeruli) separately. There was generally a Th cell predominance except the most unfavorable rejection type, the acute vascular rejection (AVR), where the Tc cells outnumbered all other infiltrating cell populations. The most macrophages too were detected in AVR. The high proportion of plasma cells in chronic rejection indicate an important role of the humoral immune response in this type of rejection, and could also be used as a differential diagnostic sign versus CsAN.

Graft Rejection

Demonstration of bacterial antigen in macrophages in experimental pyelonephritis.

The immunomorphological characteristics of interstitial macrophages with PAS-positive granules were studied in experimental Escherichia coli pyelonephritis in rats, using an anti-E. coli antibody. Immunohistochemical, immunoelectron microscopical, as well as light- and electron microscopical findings were compared at twelve time points between 2 days and 13 weeks after infection. Macrophages with PAS-positive granules were present in the inflammatory infiltrates from the 7th day. The granules were phagolysosomes, filled predominantly with myelin figures. The myelin figures originated mainly from the constituents of the bacterial wall and reacted with the anti-E. coli antibody even 13 weeks after infection. The storage of bacterial residues with preserved antigenic structures for several weeks after infection indicates disturbed phagolysosomal elimination of the bacterial substances in the PAS-positive macrophages. In the formation of macrophages with PAS-positive granules, lysosomal overloading with large amounts of bacteria and cell debris is assumed, leading to consumption of the lysosomal enzymes, consequent incomplete breakdown and retention of the bacterial residues.

Animals

[Fibrolamellar liver carcinoma].

Four fibrolamellar liver carcinomas were surgically removed and were postoperatively examined. Three patients are alive roughly three years from surgery, and there are no signs of imminent recurrence, while the fourth case was diagnosed only two months back. The carcinomas had developed in non-cirrhotic livers which also produced negative responses to serological tests for hepatitis B. In flow cytometry, DNA indices were indicative of diploidy in two cases and aneuploidy in the other two. The highest DNA index value was recorded from the smallest tumour which could be assigned to the category of "minute HCC". No correlation was found to exist either between age, sex, and DNA index. Positive CEA reaction was immunohistochemically recorded from few tumour cells, whereas negative AFP responses were exhibited by all four tumours. Appearance of AAT in tumour cells was detected in three cases. High degree of differentiation, similarity between tumour and liver cells, and oncocytoid nature of cells were revealed by optical light and electron microscopy. This high degree of differentiation was additionally confirmed by two factors: glucose-6-phosphatase activity was preserved in all four tumours, adenosinetriphosphatase activity was histochemically detectable from certain points of the tumour cell membrane. Gamma-glutamyl-transpeptidase activity, too, was very strongly pronounced in all tumour cells, which, however, cannot be interpreted as a sign of differentiation. Membrane-bordered "dense-core" granules were visible in few tumour cells in two cases. Intensive granular serotonin reactions were immunohistochemically recorded from the majority of tumour cells in the same cases. Our histochemical and ultrastructural parameters have produced clear-cut evidence to the hepatocyte nature of FLC cells. Yet, the presence of secretory granules and positive serotonin reaction might possibly support the assumption that the FLC originates from those pluripotent cells of the liver which may develop in two directions, depending on the individual case, to become either hepatocytes or neurosecretory cells.

Adolescent

[Pathomechanism of the development of chronic obliterative transplantation arteriopathy in human kidney allografts].

Authors examined cells participating in intimaproliferation in transplantation arteriopathy ultrastructurally in needle and wedge biopsy material from 40 transplanted kidneys, and immunohistochemically in 10 cases. In early biopsies--even in two control kidneys--it could be observed that the smooth muscle cells of media are in direct contact with endothel cells by their small processes. Processes can fulfil a receptor function and can transmit endothel noxa to smooth muscle cells. Smooth muscle cells of media react to endothel damage caused by rejection with migration to intima and during this period they are transformed to myofibroblasts (myointimal cells). In the mean time inflammatory cells (mainly macrophages, helper and cytotoxic cells in lower number) from the lumen infiltrate the intima, and mediators, enzymes released from them can inspire smooth muscle cells to further proliferation, migration to intima and transformation to myofibroblast. To effect of mediators (gamma interferon) released from inflammatory cells, the myointimal cells during rejection will press out 2nd class transplantation antigens (HLA-DR), and as vicious circle it further aggravates immune reply to graft, causing vascular damage, intimaproliferation.

Chronic Disease

[A case of ceruminous adenocarcinoma. Ultrastructural and immunohistochemical studies].

Case of ceruminal adenocarcinoma is reported. Tumor was diagnosed in advance stage, and within a month following diagnosis it caused death. Tumor started from right auditory canal, undermined the pyramidal bone and infiltrated great part of right side of base of skull, narrowing great foramen to a certain extent. Metastasizes were only the right of dura. Besides electron microscopic studies, authors performed the immune-histochemical and lectin-histochemical examination of tumor the first time.

Adenocarcinoma

[Recurrence of focal sclerosing glomerulonephritis in the kidney graft].

This is the first report on the recurrence of a glomerular disease in renal transplant in Hungary. The primary disease of the girl died at the age of 13 was focal sclerosing glomerulonephritis with slight mesangial cell proliferation. The first symptoms appeared at the age of 6.5 and they progressed rapidly. Four years later, because of the severe nephrotic syndrome and chronic renal failure, renal transplantation was performed with the synchronous removal of the patient's own kidneys. In the latter an interesting immunohistological finding has been observed: beside the usual positivities, the basement membrane of the distal tubule at the opposite side of the macula densa showed a strong reaction with anti IgM and a somewhat weaker positivity with anti C3 sera. The primary disease recurred very soon. A mesangial cell proliferation, however did not develop, in contrary to the primary disease, which contradicts the theory that the mesangioproliferative form would be a distinct clinicopathological entity.

Child

Bilateral renal malacoplakia in systemic lupus erythematosus and adrenogenital syndrome.

We report a case of an 8-year-old girl with adrenogenital syndrome secondary to adrenocortical hyperplasia. Thirteen years later systemic lupus erythematosus developed with lupus nephritis. In spite of complex continuous immunosuppressive therapy, she died from terminal renal failure. At autopsy, extensive bilateral renal malacoplakia was discovered. The role of recurrent urinary tract infections and of immunological disturbances in the pathogenesis of malacoplakia is discussed.

Adrenal Hyperplasia, Congenital