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Biomedical subjects

P Rossmann

Publications and source records attributed to P Rossmann.

At least 37 records · Page 2Linked to original sources
PubMed1997

[Charge interactions of immune deposits in glomeruli (experimental study)].

An i.v. injection of 8-40 mg (kg cationized and heat-aggregated rabbit or human Ig (cat-aggr RIg,-HuIg; pI 9.5) elicited a strong diffuse linear fixation in rat glomerular capillaries revealed by one-step immunofluorescence or immunoenzyme histochemistry 1 and 2 h post-injection. Preferential binding to the lamina rara externa (LRE) was documented in ultrastructure by preembedding and postembedding assays (HRP-coupled antibody and protein A-colloidal gold, respectively). After 24 and 48 h the glomeruli were negative. Polyethylenimine (PEI)-reactive polyanion of LRE was significantly reduced 1 h after cat-aggr-Ig; depletion persisted even after 48 h. Non-cationized Ig aggregates did not bind to the glomerular capillaries. A subsequent i.p. injection of swine anti-rabbit-Ig antibody (SwAR, 15 mg i.p. after 4 h) produced the same linear binding of both two antigens which, however, persisted after 10 days and assumed a granular pattern. After presensitization with RIg (1-2 mg i.p. or s.c.; 4 days before cat-aggr RIg) the early linear fixation underwent a gradual transformation into the granular pattern and deposits of mesangial, rarely of epimembranous type were found 1 week after cat-aggr RIg and later. RIg and SwIg were proved in both types of deposits. After 2 weeks both rat Ig and C 3 were present, too. Rarefaction of deposits and their concentration in the vascular poles took place during 3 months, and deposits also appeared in the media of vas afferens. The antigen load did not produce an acute glomerulonephritis or significant proteinuria; slight focal mesangial sclerosis and a discrete increase in serum creatinine were noted after 2-3 months. To sum up: The one-shot charge interaction is prompt but short-lived whereas the local binding of additional proteins, especially after a specific preimmunization, significantly prolongs the contamination of glomeruli and promotes the build-up of immune complex-type deposits which gradually retreat to the mesangial stalk and vascular pole.

Animals↗
PubMed1995

Molecular mimicry as a possible cause of autoimmune reactions in celiac disease? Antibodies to gliadin cross-react with epitopes on enterocytes.

Structural similarities between external antigen and self components are believed to be one of the possible causes of autoimmunity. This study describes the presence of similar structures shared by gliadin and enterocyte surface molecules recognized by antigliadin mAbs. The reactivity of mAbs to gliadin was followed by ELISA using fixed enterocytes, their brush-border membranes, or purified enterocyte antigen. The specificity of reaction was confirmed by ELISA inhibition studies and by immunohistochemical staining of rat tissue sections using biotin-avidin-peroxidase technique. Immunoprecipitation analysis of 125I-labeled intestinal epithelial cells using antigliadin mAb revealed the presence of two main cross-reactive molecules of 28 and 62 kDa. The 62-kDa and an associated 66-kDa protein were isolated by affinity chromatography. Immunoblotting analysis showed that a 28-kDa protein detected by immunoprecipitation also reacted with IgA of celiac disease patient sera.

Animals↗
PubMed1994

[Early changes in vascular graft rejection in transplanted kidneys: the past and the present].

BACKGROUND: With maintenance azathioprine+prednisone and in biopsies performed exceptionally earlier than in the 4th week (1966-1984, 476 cadaveric kidney transplantations), prevalence of obliterative arteriopathy (OA, transmural arteritis, 4/III/v3 Banff classif.) was 22.1%, with graft loss by rejection within 6 mos. in 89.4%. The aim of this analysis was to study prevalence and prognostic importance of the former and of further early vascular lesions in subjects with maintenance cyclosporin A using biopsies performed as early as in the 1st week. METHODS AND RESULTS: In a retrospective study on 449 transplantation (1987-92, cyclosporin A+prednisone+azathioprine, 64.7% grafts histologically--mostly repeatedly--examined), prevalence and prognostic classification (A-good, B-uncertain, C-poor prognosis) in recipients with OA, with cellular arteriopathy (CA, intimal arteritis, 4/II-III/v2-v3 Banff classif.) and with minimal arterial lesions (MZ) were assessed. Prevalence of OA was found to be 7.1% transplantations, with graft loss by rejection within 6 mos. in 71.9%, and with A:C proportion 25.0%: 62.5%. CA was found in 5.1% and showed A:C proportion 34.7%: 34.7%; in 6/13 cases with repeated histology, OA was later encountered, which is a strong point against its humoral pathogenesis. Prevalence of MZ was 10.9%, with A:C proportion 40.8: 4.1%. CONCLUSIONS: Both OA and CA are related to rejection, while the etiology of MZ remains to be clarified. With cyclosporine, prevalence of OA markedly decreased and its prognosis somewhat improved; secondary prevention is possible when an early diagnosis (early and repeated biopsies) is done and immediate treatment (antilymphocyte globulins) started.

Graft Rejection↗
PubMed1994

[Kidney transplantation and tumors].

BACKGROUND: In conjunction with organ transplantation and subsequent treatment there is a number of influences which potentiate the development and possibly the growth of tumours. This applies naturally also to transplantations of the kidneys. The objective of the present study was to assess the frequency and type of tumours in patients after renal transplantation and compare these results with data of the at present most extensive worldwide register in Cincinnati (CTTR). METHODS AND RESULTS: The authors analyzed a group of 879 patients where within the period between March 21, 1966 and Sept. 29, 1992 a total of 989 renal transplantations were performed from dead relations-934 or from living relations (55); in 38 patients combined transplantations of kidney and pancreas were performed. The group comprised 59% men and 41% women. In the course of years the pattern of prophylactic immunosuppression changed: up to 1984 the basic drug was azathioprin combined with prednisone, during the same year cyclosporin A was introduced as a rule in a triple combination with azathioprin and prednisone; less frequent was the combination of cyclosporin A and prednisone. For antirejection treatment corticoids were used, later supplemented with polyclonal or monoclonal antibodies. During the period 1966-1992 tumourous diseases were diagnosed in 32 patients (3.64%); in two of these patients; combined transplantation of the kidney and pancreas was performed (5.3%). There was no difference in the frequency of tumours in patients with immunosuppressive medication (azathioprin with prednisone-3.80%) and cyclosporin A (3.51%). The mean age of the patients at the time of diagnosis of the tumour was 50.2 years, the interval after transplantation was 42.2 months (in patients treated with azathioprin 57 months, in the group treated with cyclosporin A 29.2 months). As far as the location of tumours is concerned, tumours of the skin predominated 25% (as compared with CTTR where it was 30%), tumours of the patient's own kidneys 21.9% and of the urinary pathways 15.6%, tumours of the gastrointestinal tract 12.5%, lymphomas in 9% (as compared with 15-20% in CTTR), tumours of the lungs 6.25% and other localizations also 6.25%. Some tumours frequently encountered in the population (lung cancer, cancer of the prostate, breast, colorectal carcinoma) are less frequent in patients after transplantation (CTTR); however, this fact was not confirmed by the authors. In renal tumours and tumours of the efferent urinary pathways data on analgetic nephropathy were encountered very frequently. CONCLUSIONS: The prevalence of tumours of various organs in patients after transplantations of the kidneys are not a frequent but a very serious complication. Its causes are multifactorial. The group after renal transplantations in the Czech Repubic has some deviations as compared with CTTR as regards affection of organs.

Female↗
PubMed1994

[Therapy in kidney transplant rejection using murine monoclonal IgG2a A1CD3 (Cedetrin)].

BACKGROUND: One of the substances used in recent years to suppress immune reactions after organ and tissue transplantations is mouse IgG2a globulin which acts selectively on CD3 lymphocytes; it is known under the name of Orthoclone (Ortho Co.) An analogous preparation was developed in the Institute of Molecular Genetics, Academy of Sciences, Czech Republic, although the idiotype is different. The authors submit a report on the experience with treatment of rejection of transplanted kidneys. METHODS RESULTS: Monoclonal mouse globulin IgG2a (Cedetrin) was administered to 20 patients after renal transplantation on account of a rejection episode or progressing rejection; the mean interval after transplantation was 16.1 (range 0.25-96) months; the rejection episode or progressing rejection responded little in the majority of patients to 6-alpha-methyl prednisolone (Urbason, Hoechst, Solu-Medrol, Upjohn). For prophylactic immunosuppression the following combinations were used: cyclosporin + azathioprine + prednisone (17x) or azathioprine + prednisone (3x). Cedetrin was administered by the i.v. route in two to 11 doses a 3 mg substance. Of 20 patients in 6 Cedetrin administration had to be discontinued (allergy, infection, leucopenia, hyperhydration). In 14 the tolerance was satisfactory, the type and frequency of side-effects was similar as after Orthoclone; the antibody formation was less frequent. The specificity of Cedetrin as regards its action on T lymphocytes was confirmed. The effect was good to very good in 6 of 8 patients where the rejection filtrate was histologically active. In 9 patients treated during the first year after renal transplantation the cumulative survival of the graft at the end of the 12th, 24th and 36th month following transplantation was 89%, 67% and 56% resp. Because the therapeutic effect depended on histologically proved rejection activity, the authors consider biopsy of the graft before Cedetrin treatment essential. CONCLUSIONS: The therapeutic administration of monoclonal mouse globulin IgG2a A1CD3 (Cedetrin), developed in the Institute of Molecular Genetics, Academy of Sciences, Czech Republic, produced by Exbio Co., CR) has a favourable effect on rejection episodes or progressing rejection of transplanted kidneys. Treatment is indicated in confirmed histologically active rejection.

Adult↗
PubMed1994

[Etiopathogenesis of insudative vasculopathy in transplanted kidneys].

In 99 renal allograft recipients with insudative vasculopathy of graft, mean serum cholesterol levels, prevalence of subjects with hypercholesterolaemia, mean cumulative doses of methylprednisolone, prevalence of subjects with methylprednisolone doses > or = 6,000 mg and prevalence of patients with hypertension, all in the period between transplantation and the first diagnostic biopsy, were compared between 51 those with conventional and 48 with cyclosporine maintenance immunosuppression. In subjects treated with cyclosporine the lesion was found in biopsies performed sooner and was present more frequently, prevalence of hypercholesterolaemia and of hypertension was similar and that of subjects with both hypercholesterolaemia and hypertension lower than in subjects treated with azathioprine. A positive correlation was present between high doses of methylprednisolone and prevalence of hypertension, regardless of the type of immunosuppression and of severity of vasculopathy. In etiopathogenesis of insudative vasculopathy atherogenic factors are most probably involved, more markedly when azathioprine is used for maintenance immunosuppression. With cyclosporine, changes of graft haemodynamics and possibly also toxic damage to the vessels involved seem to be more important.

Arteriosclerosis↗
PubMed1994

On the postnatal growth of the canalis mandibulae in the miniature pig.

The shape and the growth of the canalis mandibulae in female miniature pigs, MINI-LEWE, were analysed in 11 postnatal age steps. The lower jaw halves were cut frontally in a defined position and the heights and widths of the canalis mandibulae were measured. Changes in the shape of the canalis mandibulae in the frontal saw cuts were observed with regard to the dentition. After the eruption of the deciduous teeth there was no further change in shape. Growth curves of the mandibular canal's measures reached a peak during the eruption of the deciduous teeth and the first molar, decreasing significantly afterwards. A close correlation was observed between the measures of canal height and canal width. On the other hand there was only a slight correlation with the external measures of the mandible, which suggests that there are different growth processes.

Aging↗
PubMed1993

[Graft rejection after changing from cyclosporin A therapy to conventional treatment in kidney transplant patients].

Hundred and twenty live patients after the first transplantation of the kidney from a decreased donor with satisfactory graft function, treated with cyclosporine A combined with prednisone or combined with prednisone or combined with prednisone and azathioprine were divided into three groups: A--20 patients changed during the 6th-9th month after transplantation to conventional azathioprine-prednisone treatment. B--68 patients switched to this treatment during the 10h-15th month following transplantation. K--37 patients who were not switched to other treatment during the mentioned period. Within 3 months after the switched rejection develop in 21% of the patients in group A and 20% patients in group B. The incidence of rejections during a comparable period in group K was significantly lower (3%), as compared with group A and insignificantly lower (14%), as compared with group B. The majority of rejections was documented by biopsy but no morphological difference was found between rejections which developed in patients switched and not switched to other treatment. It was striking that there was a difference, though insignificant, in the sensitivity of rejections to antirejection treatment with methylprednisolone after switch to a different preparation: in group A 25%, in group B 37% and in group K 80%. Patients in group A with rejection after the switch had developed a rejection even before the switch significantly more frequently (in 75%) than in group B (in 7%) and these rejections led significantly more frequently to loss of the graft.

Adult↗
PubMed1993

[Rapidly progressing glomerulonephritis with antibodies to glomerular capillary basement membrane].

Antiglomerular basement membrane glomerulonephritis was diagnosed in 14 patients (6 men and 8 women) aged 20 to 59 years. Five patients were found to have Goodpasture s syndrome. 5 rapidly progressive glomerulonephritis. 1 nephrotic syndrome, and 1 had mild glomerulonephritis. Blood pressure, proteinuria and haematuria were not severe in most patients. In 10 patients, the diagnosis was not established before end-stage renal failure had developed. Four patients died of lung haemorrhage, in 3 the haemorrhage was controlled by the treatment, in 3 renal failure without lung haemorrhage occurred, and in 3 renal function improved or was stable. The prognosis improved significantly after plasma exchange together with immunosuppression had been introduced.

Adult↗
PubMed1993

Experimental adriamycin nephropathy. Fine structure, morphometry, glomerular polyanion, and cell membrane antigens.

Two doses of adriamycin (2 mg/kg i.v.) were administered to young adult rats with a 22-day interval and the kidneys were examined 51, 79, and 107 days after the first injection. Light microscopy showed early prominent intraglomerular microcystic spaces and progressive, though not severe, segmental glomerulosclerosis with focal interstitial scarring and round-cell infiltration. The main features of the ultrastructure were widespread fusion of foot processes, focal cytoplasmic rarefaction of podocytes, and non-specific sclerosis of the mesangium without signs of severe degenerative changes or mesangiolysis. The segmental microcystic structures corresponded to agglomerated intrapodocytic vacuoles. The scatter of glomerular polyanion sites visualized by polyethylenimine-phosphotungstic acid resembled that of control animals but the quantitative assessment revealed a significant reduction. CD4-positive cells were the predominant element of the interstitial infiltrates. Most of the infiltrating cells expressed Ia antigens, whereas Ia-positive intraglomerular resident mononuclear cells were depleted. The adriamycin lesion resembles the post-five-sixths nephrectomy ablation nephropathy in the subpopulations of the interstitial infiltrate but differs from it in the reduction of intraglomerular resident macrophages, the absence of destructive mesangial damage, and reduced segmental glomerulosclerosis. The main feature is the prolonged damage of podocytes, especially of their cytoskeletal system.

Animals↗
PubMed1992

[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↗
PubMed1992

[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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1991

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↗
PubMed1990

[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↗
PubMed1990

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↗