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Biomedical subjects

P Rossmann

Publications and source records attributed to P Rossmann.

At least 19 recordsLinked to original sources

[Long-term prognosis in chronic primary glomerulonephritis in relation to urinary findings].

A long-term followed-up group of 993 patients with primary glomerulonephritis (GN) was divided by urinary syndromes, defined according to the degrees of proteinuria and haematuria. Responding morphological diagnoses and prognoses were found for each urinary syndrome. Isolated and predominant haematuria were determined as benign, with stationary course even without immunosuppressive therapy. The prognosis of isolated, even moderate, proteinuria is more serious finding. Its relevance increases with the degree of haematuria. Severe combined proteinuria and haematuria is the most serious urinary syndrome. Both proteinuria and haematuria may be changing in the course of GN and increasing proteinuria points to the future glomerular filtration rate decrease.

Chronic Disease

[IgA nephropathy. Morphology, clinical picture and significance of mesangial fibrin deposits].

IgA nephropathy was diagnosed in 114 biopsies from 107 patients comprising 78% men. Light microscopy revealed most frequently mild proliferative glomerulonephritis with frequent though rudimentary extracapillary proliferation (in one quarter of the biopsies). Allergic manifestations in the case-history were recorded in 14% of the patients. Almost in one third of the patients the disease started by macroscopic erythrocyturia. A typical finding in urine was predominating erythrocyturia (tens of millions in Addis sediment) over proteinuria (usually less than 1.5 g/24 h). Cumulative "renal survival rate" ten year after biopsy was 84%, the cumulative ratio of remissions was 30%. Mesangial fibrinoid deposits were found in half the patients with a severe course of the condition.

Adult

Arteriolosclerosis of the human renal allograft: morphology, origin, life history and relationship to cyclosporine therapy.

In the decade 1979-1988, 658 biopsies were collected from 568 cadaveric renal allografts. In 118 grafts a non-proliferative insudative vasculopathy (IVA) was found in afferent vessels. Immunosuppression was based on azathioprine (AZA) or on cyclosporin A (CsA), from 1983. The prevalence and extent of IVA has increased significantly since 1984. Light microscopy showed fibrinoid and hyaline masses of varying extent; transmural insudative "knobs", intimal oedema with metachromasia, and microthrombosis were also seen with CsA. The ultrastructure of the insudates was unremarkable but CsA grafts displayed early oedema and hypergranulation of endothelial cells with a disarray of smooth muscle cell (SMC) microfibrils, and pronounced degenerative changes of SMC. Rebiopsy showed stationary IVA in AZA grafts and progression in one-half of CsA-treated patients. Nephrectomy specimens revealed, however, a marked predominance of late rejection endarteritis; in only 3 cases was IVA and/or microthrombosis the possible cause of nephrectomy. The mean donor age was higher in severe IVA in CsA grafts and the mean post-transplantation interval at the time of diagnosis of IVA was significantly shorter in CsA-treated patients. No important differences in cumulative graft survival were seen between grafts with absent, moderate or severe IVA. Unused cadaveric donors' kidneys of comparable age exhibited normal arterioles or a slight focal insudative or hyaline lesion.

Arteries

Detection of antigen in the coelomocytes of the earthworm, Eisenia foetida (Annelida).

Earthworms, Eisenia foetida, are able to respond to antigenic stimulation by the formation of the antigen-binding molecules by coelomocytes--the effector cells of annelids' defence reactions. The ability to react with gold-labelled antigen was detected in agranular coelomocytes by electron microscopy. Furthermore, flow cytometry analysis used for quantitative evaluation of antigen binding showed significant increase of both antigen-binding cells and the amount of antigen bound per cell after stimulation. The antigen binding was inhibited by preincubation of cells with several similar proteins, although the most potent inhibitor was the immunizing antigen.

Animals

The effect of polyamines on the endothelium and vascular wall metabolism in the rat.

Administration of putrescine, a polyamine, to rats leads to endothelial injury manifesting itself by an increased number of endothelial cells circulating in blood. Moreover, putrescine affects the metabolism of the arterial wall itself, primarily by increasing the activity of phosphomonoesterases I and II and by decreasing the activities of Krebs cycle enzymes, both of which are phenomena that can be regarded as "preatherogenic" changes 5, 6, 8, 11 preceding the onset of pathological processes in the arterial wall. Putrescine significantly decreases aortic ATPase (adenylpyrophosphatase) both in the acute and chronic phases of experiment. Ultrastructural changes after 16 weeks of putrescine administration manifested themselves in increased proliferation and smooth muscle cell injury eosinophil inflitration into the adventitia. The findings support the hypothesis that high levels of PA in homocysteinemic patients and those on chronic dialysis are a common denominator accelerating atherosgenesis in these subjects.

Animals

[Type I and III membranoproliferative glomerulonephritis. Clinical picture and prognosis].

Membranoproliferative glomerulonephritis (CN) of types I and III was diagnosed in 154 patients (15.5% out of primary CN). Out of this number 60% were men. During biopsy, one third of the patients were normotensive, 40% were slightly hypertensive and one third suffered from severe hypertension. Mean proteinuria was 6.5 +/- 5.5 g/24 h. In two thirds of the patients erythrocyturia was higher than 35 mil. in Addis' sediment and the findings in the urine were characterised by the proportion between proteinuria and erythrocyturia (p less than 0.001). During biopsy in one half of the patients, the serum creatinine level was already elevated. The presence of creatininemia was found to be directly linked to blood pressure, proteinuria, the degrees of extracapillary proliferation, tubulointerstitial regression and vascular arteriolosclerosis. The cumulative duration of the kidney function within the period of 10-20 years was 41 or 28%, the cumulative cure amounted to 14% 10 years after biopsy.

Adolescent

Experimental ablation nephropathy. Fine structure, morphometry, cell membrane epitopes, glomerular polyanion and effect of subsequent transplantation.

The subtotal (5/6) nephrectomy performed in 23 adult female rats induced severe hypertrophy of residual parenchyma with interstitial fibrosis, tubular dilatation, and focal and segmental glomerulosclerosis (FSG). This ablation nephropathy (AbN) caused proteinuria, progressive renal failure, and hypertension. The extent of FSG was assessed by semiquantitative scoring. The ultrastructure revealed widespread foot process fusion, many dense cytoplasmic inclusions in podocytes, and degenerative changes or disruption of mesangium with glomerular "microcysts". Numerous granular deposits of rat Ig were seen in the glomeruli but a short praeterminal i.v. load by heat-aggregated human Ig did not alter the morphology of AbN and produced discrete and inconstant glomerular deposits. Similarly an i.v. injection of protamine and heparin generated protamine-heparin complexes seen in various layers of glomerular capillary wall, similar to those found previously in normal rats. AbN displayed a partial irregular depletion of polyanion sites reactive with polyethylenimine in lamina rara externa. A significant increase in both glomerular and interstitial Ia+ cells and a marked predominance of W3/25+ cells in the interstitial infiltrates were documented by immunohistochemistry in the remnant kidneys. Both AbN and FSG could be largely corrected (or prevented?) by subsequent syngeneic renal transplantation (TPL; 6 animals). On the other hand a severe AbN was found in two post-ablation residues after unsuccessful TPL with graft necrosis or sclerosis.--AbN has some analogies to various chronic human nephropathies (e.g. FSG) and may explain their progression to the terminal failure. Degenerative and finally destructive mesangial lesion seems to be of prime importance in AbN.

Animals

[Idiopathic membranous glomerulonephritis. Clinico-morphologic relations and prognosis].

Membranous glomerulonephritis (GN) was diagnosed in 61 of 993 patients with histologically confirmed primary GN. Two-thirds of the patients were men. High hypertension was recorded in 7.5% of the patients. A typical finding was marked proteinuria (6.15 +/- 4.88 g/24 h.) with mild erythrocyturia (median 8 million in Addis sediment). At the time of biopsy 86% of the patients had normal creatininaemia, the level of which was positively correlated with the blood pressure and degree of tubulointerstitial regression. The cumulative duration of renal function in 5, 10 and 20 years was 88, 80 and 57%; during the same time intervals 22, 48 and 52% of the patients were cured.

Adult

Detection of cationic and non-cationic markers in the rat glomerulus by electron probe analysis.

Acidic glycans (glomerular polyanion substances) in the rat kidney were visualized ultrastructurally by three cationic markers: colloidal iron, ruthenium red, and polyethylenimine-phosphotungstic acid (PEI-PTA). Heavy metal atoms (Fe, Ru and W) were detected in ultrathin sections by energy-dispersive electron probe microanalysis (EPMA). Characteristic peaks of the locally bound elements were obtained in spectra derived from the dense structures seen by transmission electron microscopy (TEM)--i.e. the glycocalyx of podocytes and/or the polyanion sites in the lamina rara externa of the glomerular basement membrane. Weaker signals were emitted by some extraglomerular structures. This finding may reflect a low concentration of glycans in structures lacking apparent density by TEM, and/or incomplete specificity of the markers, partial dislocation of reactive substances or the presence of an endogenous element (Fe). Experimental argyrosis was elicited by the peroral administration of silver nitrate. Dense Ag precipitates were seen chiefly in the lamina densa and characteristic peaks of silver were displayed in this site by EPMA, and was best demonstrated in non-contrasted sections. A single i.v. injection of Ag proteinate failed to produce glomerular pigmentation. The only dense granular product in tubular cells yielded characteristic peaks of Fe (endogenous siderosomes) but EPMA excluded detectable amounts of silver.

Animals

[The inadequate status of information of interested lay persons about the educational campaign regarding risk factors for cardiovascular diseases].

181 interested individuals (75 males, 106 females; range 16 to 84 years) responded to a questionnaire issued by the Styrian Cardiovascular Lay Society. The main topic of the questionnaire concerned information gained via media, about the possible risk factors related to cardiovascular diseases and about any changes in life style consequent to this information. The results show that the general knowledge in this field especially in younger subjects is disappointing and that there is need for further intensive information and education.

Adolescent

Different handling of antigen by macrophages of low-responder C57BL/10ScSn strain and high-responder A/J strain of mice. II. Antigen uptake.

The uptake of 51Cr-SRBC and 125I-ARS-BG6 in the liver and spleen of non-immune low IgG responder C57BL/10ScSn mice is higher than in the high-responder A/J strain. After immunization with SRBC, the uptake in the spleen of A/J mice is ten times higher and that in the liver three times higher than in C57BL/10ScSn mice. The higher uptake of the well responding A/J strain, which is antigen specific, is due not only to a higher level of opsonizing antibodies. Endotoxin stimulation, which increases the IgG formation of the low-responding strain, does not increase the uptake in this strain. In the low-responder strain there is a considerable level of free 51Cr in the serum and kidney within 5 min after antigen injection, suggesting a high catabolic rate of the antigen. In contrast, at that time in the A/J strain virtually all of the radioactivity is still bound to the erythrocyte fraction. Ultrastructural observations suggest that in the low-responding strain the antigen residues survived in macrophages for a long period of time. The results provide evidence of differences between the metabolic activity of macrophage populations of both strains which could be related to the low IgG response of the strain C57BL/10ScSn.

Animals

[Status of information of interested lay persons: results of a questionnaire survey by the Styrian Heart Association].

181 interested individuals (75 males, 106 females; range 16 to 84 years) responded to a questionnaire issued within the information and instruction courses of the Styrian Cardiovascular Non-professional Society. The main topic of the questionnaire concerned information gained via media, possible risk factors leading to cardiovascular diseases and any changes in living conditions due to such facts. The results show clearly that the general knowledge in this field especially in younger subjects is disappointing and further intensive information and instruction would be urgently required.

Adolescent

Antibody-directed affinity therapy applied to the immune system: in vivo effectiveness and limited toxicity of daunomycin conjugated to HPMA copolymers and targeting antibody.

The applicability of targeting therapy intervention in lymphatic tissue was studied. The effect was measured as the inhibition of anti-sheep red blood cell antibody response expressed in plaque-forming cells. Daunomycin was used as the effective drug and polyclonal and monoclonal anti-Thy 1.2 or anti-Iak antibody served for targeting. Both components were coupled to a soluble N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer with oligopeptidic side sequences which permitted a controlled release of the drug in the target tissue. HPMA copolymer conjugates with side sequences Gly-Phe-Leu-Gly cleavable by lysosomal enzymes decreased in vivo the antibody reaction by 60-85%. A comparable amount of free targeting antibody was without a significant effect. Injection of targeted daunomycin decreased the toxicity of the drug against hematopoietic precursors in bone marrow colony-forming unit-spleen 80 times compared to the same amount of free drug. The in vivo effectiveness of targeted daunomycin was confirmed morphologically. Application of free daunomycin lead to a significant irritation of Kupffer cells in liver while none of the daunomycin-antibody-copolymer conjugate had such an effect.

Acrylates

Failure to detect the presence of pluripotential haemopoietic stem cells in the mouse brain.

Single cell suspensions prepared from adult mouse brains were tested for the presence of pluripotential haemopoietic stem cells (colony-forming units, CFU) by transfer into an irradiated recipient and enumeration of the CFU in the recipient's spleen. In contrast to the findings of others (Bartlett, 1982), we did not detect CFU after injection of brain cell suspensions, although they were detectable after inoculation with bone marrow cells. The number of CFU in recipients after transfer of increasing numbers of brain cells was the same as that detected in the irradiated controls which had not received any transferred cells. Finally, cells from the brain, in contrast to bone marrow cells, were not able to protect recipient animals from the effects of lethal irradiation.

Animals

Protein aggregates in extracorporally perfused rabbit kidneys.

Eighteen rabbit kidneys were perfused ex vivo for 1 h with allogeneic blood, and in 16 a solution of xenogeneic aggregate-free, aggregated or antibody-complexed protein was added to the perfusate 5 min after the start (human immunoglobulins or serum albumin, partly cationized, were used). The kidneys were examined by light and electron microscopy and the human and rabbit immunoglobulin (or albumin) precipitates were detected by direct immunofluorescence and ultrastructural immunohistochemistry. In 13 kidneys the perfusion produced small segmental glomerular endocapillary aggregates of platelets, leukocytes, and granular precipitates reactive with both anti-rabbit and anti-human antibodies. No typical deposits were seen in mesangium or in periphery of glomerular capillaries but rabbit Ig penetrated to the inter- and subepithelial spaces of proximal convoluted tubules. Three kidneys perfused by cationized aggregated human Ig (or by cationized albumin-antialbumin complexes) exhibited a destructive lesion with rapid breakdown of blood flow and massive global endocapillary plugs of similar ultrastructure but with focal endothelial sloughing. Pericapillary granular precipitates of human and rabbit Ig were seen in these kidneys. When the blood with cationized Ig aggregates was used for perfusion of two further kidneys extensive endocapillary aggregates with endothelial damage reappeared but the extracapillary penetration and precipitation were lacking and the blood flow largely improved. Membrane polyanion of podocytes stained by colloidal iron was preserved even in close proximity of cationized complex precipitates. Thus, in the ex-vivo perfusion model the preformed neutral aggregates did not penetrate through the glomerular capillary wall and were not phagocytized by mesangial cells. The cationized aggregates induced rapid circulatory failure with massive platelet clumping and granular pericapillary "humps" ultrastructurally different from the deposits of human and experimental immune complex glomerulonephritis.

Animals

Puromycin aminonucleoside nephropathy: ultrastructure, glomerular polyanion, and cell surface markers.

Puromycin aminonucleoside nephropathy with heavy proteinuria and oedema was induced in rats by 10 consecutive daily subcutaneous injections of aminonucleoside (1.67 mg/100 g of body weight). The main ultrastructural lesions were vacuolation of podocytes and total fusion of foot processes with loss of colloidal iron-reactive polyanion layer on the epithelial surface adjacent to the basement membrane. On the other hand the outer surface of podocytes and intravacuolar granular substance stained with colloidal iron. In scanning electron microscopy of freeze-fractured tissue the swollen podocytes and the urinary spaces displayed granular and filamentous precipitates. Seven cell surface antigens were examined by indirect enzyme immunohistochemistry with a series of MRC OX monoclonal antibodies. Glomeruli of control rats exhibited rare isolated Ia- positive endocapillary cells, possibly monocytes; these elements were significantly reduced in puromycin aminonucleoside nephropathy but there was an increase in Ia- positive cells in the cortical interstitium. Control kidneys harboured scanty interstitial T lymphocytes. These latter, especially the T8- positive cytotoxic/suppressor subpopulation, were markedly augmented in puromycin aminonucleoside nephropathy. The expression of class I histocompatibility antigens and of differentiation antigens (Thy 1) was not altered by aminonucleoside.

Animals

Wegener's granulomatosis with bilateral necrotizing scleritis, polyarthritis and renal failure efficiently treated with immunosuppressive therapy.

A case report of a female patient with Wegener's granulomatosis is presented. After an initial involvement of the upper respiratory tract in the form of a sinusitis, there followed a severe necrotizing bilateral scleritis necessitating the enucleation of the left eye ball. Renal involvement developed as late as 24 months after the onset of the disease and led to renal failure within three months. Throughout the duration of her disease, the patient had joint symptoms in the form of episodes of migratory nondeforming polyarthritis. The administration of corticosteroids alone in daily doses up to 60 mg prednisone failed to control the progression of the disease, while immunosuppressive therapy with cyclophosphamide combined with methylprednisolone pulse therapy and haemodialysis resulted in a marked improvement of renal function and in the subsidence of the ocular and articular symptoms.

Acute Kidney Injury