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R P Linke

Publications and source records attributed to R P Linke.

At least 37 records · Page 2Linked to original sources
PubMed1998

Generalized AA-amyloidosis in Siberian tigers (Panthera tigris altaica) with predominant renal medullary amyloid deposition.

Generalized amyloidosis with predominant renal medullary amyloid deposition was found in four closely related Siberian tigers (Panthera tigris altaica) suffering from end stage kidney diseases. Only minimal to mild amounts of amyloid were deposited in various organs outside the kidneys with individually variable organ involvement. The Congo red staining affinity of amyloid deposits was sensitive to potassium permanganate oxidation. The deposits were further characterized as being of the amyloid-A (AA) type by immunohistochemistry using the mouse monoclonal antibody mc4 directed against a conserved region of the human AA-protein. A combination of immunohistochemistry and Congo red staining was much more sensitive for the diagnosis of amyloid deposits than Congo red staining alone. With this combination, even minimal amyloid deposits were detected that had been missed in the first reading using Congo-red-stained slides alone. Since no common primary cause was identified, the amyloidosis was classified as idiopathic generalized AA-amyloidosis with a potential familial predisposition.

Amyloidosis↗
PubMed1998

Clinical benefits of diagnosing incipient AA amyloidosis in pediatric rheumatic diseases as estimated from a retrospective study.

OBJECTIVE: The diagnosis of AA amyloidosis could not be made in eight patients with pediatric rheumatic diseases as later verified employing the more sensitive combination of Congo red and additional immunocytochemistry (CRIC). The objective of this paper is to estimate the benefit of CRIC by reevaluating the historical charts with respect to the question as to which of the diagnostic and therapeutic measures would have been altered if the correct diagnosis had been known at the time of the primary biopsy. METHODS: All subsequent biopsies of eight children with historically missed AA amyloidosis in their primary biopsies were retrieved, together with the historical data including the Congo red stains of the biopsies. The biopsies were reexamined blindly for the presence of amyloid and the results were compared with the historical data concerning diagnostic and therapeutic measures. RESULTS: Using CRIC, AA amyloidosis could be identified an average of approximately three years earlier as compared to the historical data. This gain in time would certainly have altered the diagnostic as well as the therapeutic options, i.e. 10 out of 21 biopsies would have been spared and the earlier diagnosis would have initiated more significant antiinflammatory therapy. CONCLUSION: Very early detection of amyloid reduces the diagnostic burden and unveils an option for a consequent antiinflammatory therapy very early in the course of AA amyloidosis.

Amyloidosis↗
PubMed1997

[Liver transplantation in familial amyloid polyneuropathy. Case report and review of the literature].

A 59-year old male of German origin noticed exercise-independent cardiac arrhythmia two years before admission. An alanine 47 transthyretin variant of Familial Amyloid Polyneuropathy with hypertrophic cardiomyopathy, peripheral sensory-motor polyneuropathy, I, degree AV heart block was diagnosed. To diminish production and deposition of mutant transthyretin and to prevent disease progression orthotopic liver transplantation was performed. Prior to transplant the patient complained of inappetence. Postoperatively, he received a chemically defined enteral nutrition regime that was discontinued after 30 months until return of appetite and weight gain indicated marked improvement. However, a duodenal biopsy still demonstrated amyloid deposits 24 months after transplantation. Echocardiographic findings remained unchanged. Neurologic examination showed an improvement of sensory-motor polyneuropathy with regression of electromyographic changes. Only traces of variant transthyretin were detectable in plasma samples taken 12 months after the operation. During the 3 year follow-up, no additional symptoms have occurred and progression of amyloidosis was prevented. Currently, orthotopic liver transplantation is the only specific treatment to prevent progression of familial amyloid polyneuropathy.

Amyloid↗
PubMed1997

Identification of lambda light chain amyloid in eight canine and two feline extramedullary plasmacytomas.

Amyloid deposition in varying amounts and with variable patterns of distribution (focal or diffuse) was demonstrated in eight canine and two feline extramedullary plasmacytomas expressing lambda light chains. Frequently, the neoplastic plasma cells had been displaced by the amyloid deposits. Foreign-body giant cells were regularly detected in the vicinity of the amyloid. In all 10 cases, Congo-red staining of the amyloid was resistant to potassium permanganate oxidation. Immunohistochemically, the amyloid reacted positively with cross-reacting antibodies against human and equine A lambda amyloids. Extramedullary plasmacytomas accompanied by localized AL amyloidosis have so far been described in human beings, dogs, cats and horses.

Amyloidosis↗
PubMed1997

[Organ-specific nodular pulmonary amyloidosis of the A lambda type in Sjogren syndrome].

The exclusive involvement of the lungs with A lambda-type amyloidosis in nodular dispositions in a case of Sjögren's syndrome is very rare. An immunoglobulin lambda-type light chain, benign, monoclonal gammopathy has been verified as the ethological cause. The urine concentration of paraproteins was below the detection limit of the common examination methods and could only be found immunoelectrophoretically in urine concentrated 100-200 fold. The question of a possible relationship with Sjögren's syndrome is being discussed.

Amyloid↗
PubMed1996

A new isoleucine substitution of Val-20 in transthyretin tetramers selectively impairs dimer-dimer contacts and causes systemic amyloidosis.

The most frequent form of inherited amyloidoses is associated with mutations in the transthyretin (TTR) gene coding for 127-amino acid residues of four identical, noncovalently linked subunits that form a pair of dimers in the plasma protein complex. Amyloid fibrils containing the variant and to a lesser extent the wild-type form of the TTR molecule are deposited in various organs, including peripheral nerves and the myocardium, with polyneuropathy and cardiomyopathy as major clinical manifestations. So far, more than 40 distinct amino acid substitutions distributed throughout the TTR sequence over 30 positions have been found to be correlated with an increased amyloidogenicity of TTR. Most of these amyloidogenic amino acid substitutions are suspected to alter the conformation and stability of the monomer. Here we identify and characterize by protein and DNA analysis a novel amyloidogenic Val-20 to Ile mutation in a German three-generation family. The index patient suffered from severe amyloid cardiomyopathy at the age of 60. Conformational stability and unfolding behavior of the Ile-20 monomer in urea gradients was found to be almost indistinguishable from that of wild-type TTR. In contrast, tetramer stability was significantly reduced in agreement with the expected change in the interactions between the two opposing dimers via the side chain of Ile-20. Our observations provide strong evidence for the view that amyloidogenic amino acid substitutions in TTR facilitate the conversion of tetrameric TTR complexes into those conformational intermediates of the TTR folding pathway that have an intrinsic amyloidogenic potential.

Amino Acid Sequence↗
PubMed1996

Corpora amylacea in the lung, prostate and uterus. A comparative and immunohistochemical study.

Previous studies have shown that corpora amylacea (CA) in certain organs, including the prostate, lung and uterus, are composed of amyloid. This observation raises the question of whether these amyloid deposits share a common origin or demonstrate the diversity which characterizes other amyloid syndromes. Sections of the lung, prostate and uterus from 110 consecutive autopsies of individuals over 84 years of age were studied initially using H & E and Congo red staining. CA were present in 54 cases (49%) with the prostate affected in 23 cases, the lung in 19 cases and the uterus in 15 cases. Immunohistochemistry with a panel of antibodies directed against the major amyloid fibril proteins, i.e. AA, A beta 2M, A lambda, A kappa and ATTR, yielded strong immunoreactivity of prostatic and pulmonary CA with anti-A beta 2M. Immunostaining with an antibody against cytokeratin (KL1) gave a weak reaction in a single case of prostatic CA, indicating that it is unlikely that these CA derive from cytoskeletal remnants of shedded epithelial cells. The uterine CA were not stained by any of the antibodies, suggesting that they have a different origin than prostatic and pulmonary CA. The influence of the local calcium concentration and niduses on the pathogenesis of CA is discussed.

Aged↗
PubMed1996

The classification of amyloid deposits in clinicopathological practice.

A series of 104 biopsy cases with histopathological proof of amyloid, submitted to our department of pathology over the last 19 years, were re-examined. The survey investigated the medical indication for surgery, the origin and quality of the biopsy and the clinical information as documented on the request form for histopathological examination and in hospital records. Amyloid deposits were classified using antisera directed against five major amyloid fibril proteins, i.e. AA, ATTR, A lambda, A kappa and A beta 2M and optimal conditions were sought for the reliable and early characterization of amyloid disease in clinicopathological practice. This survey revealed that 98% of the biopsy cases already suffered from a disease which was either a cause or a result of amyloidosis. In only 2% of the biopsy cases was amyloidosis detected without any clinical indication. Immunohistochemical classification of the amyloid deposits and comparison with hospital records demonstrated diagnostic pitfalls such as immunostaining of amyloid by two or more antibodies recognizing different fibril proteins, and disagreement between immunohistochemical typing of amyloid and the initial clinical diagnosis. Based on these observations we assume that the characterization of amyloid disease and its biological significance is impossible in clinicopathological practice without clinical information or without immunohistochemical classification of the fibril protein in biopsy specimens. Different aspects of histopathological detection of AA- and AL-amyloidosis are discussed.

Adult↗
PubMed1996

Generalised AA-amyloidosis in a bat (Pipistrellus pipistrellus).

Generalized amyloidosis was found to be the cause of death in a female adult insectivorous pipistrelle bat (Pipistrellus pipistrellus) after chronic wound inflammation. Large amounts of amyloid were detected in liver, spleen, kidneys, stomach, intestine, lymphatic tissues, and endocrine and salivary glands. Congo red staining and green birefringence identified amyloid; the Congo red staining was sensitive to potassium permanganate oxidation. The amyloid was further classified immunohistochemically. The deposits reacted with two anti-human-AA-amyloid monoclonal antibodies in a peroxidase-antiperoxidase reaction, whereas no reaction was found with antibodies specific for other types of amyloid. Thus, the bat amyloid deposits were identified as generalized reactive AA-amyloidosis.

Amyloidosis↗
PubMed1996

Meningocerebrovascular amyloidosis associated with a novel transthyretin mis-sense mutation at codon 18 (TTRD 18G)

We describe a novel transthyretin mutation at codon 18 where Asp is replaced by Gly (D18G) in a Hungarian kindred. This mutation is associated with meningocerebrovascular amyloidosis, producing dementia, ataxia, and spasticity. Fifty different transthyretin mutations are related to amyloid deposition, typically producing a peripheral neuropathy or cardiac dysfunction. These symptoms are absent in this family. Up to now, amyloid-beta (A beta), cystatin C, and prion proteins have been known to be deposited as amyloid in the brain, leading to stroke or dementia. With this report we establish that transthyretin amyloid deposition can also produce central nervous system dysfunction as the major clinical symptom.

Amino Acid Sequence↗
PubMed1995

Deficient ferritin immunoreactivity in visceral organs from four patients with Niemann-Pick disease type C.

Ferritin, the major iron storage protein, was found to be undetectable on immunoblot analysis of spleen and liver extracts from four patients with Niemann-Pick disease type C (NPC). The patients had died from different clinical forms of this storage disease of still unknown etiology. The absence of ferritin immunoreactivity was shown using two different antisera, raised in rabbits, against ferritin from human spleen containing predominantly light-chain subunits (L-ferritin). Further evidence of absent L-ferritin in visceral tissues was provided by immunohistochemical studies performed in one of the four NPC patients. However, heavy-chain and light-chain ferritin mRNAs could be identified in cultured fibroblasts from this patient. The finding of deficient ferritin immunoreactivity is suggestive of an additional biochemical abnormality that is as marked as the known impairment of the transport of exogenously derived cholesterol in this complex lysosomal storage disorder.

Animals↗
PubMed1995

Progressive liver failure in a patient with adult Niemann-Pick disease associated with generalized AL amyloidosis.

We report a case in which an adult form of Niemann-Pick disease (type B of NPD) was associated with a rapidly progressive generalized AL amyloidosis of kappa type. Both diagnosis were made by biopsy, the NPD by bone marrow biopsy and fibroblast culture, the amyloidosis by liver biopsy. Malignant non-Hodgkin lymphoma was not found. The patient, a 67-year-old woman, died from hepatic coma subsequent to a progressive liver failure. We discuss possible relations between the lysosomal storage disease and the development and rapid progression of amyloidosis.

Aged↗
PubMed1995

Ureteral amyloid deposits of beta 2-microglobulin origin in both kidney recipients of 1 donor.

We report on 2 renal transplant recipients with ureteral amyloid deposits, each of whom received 1 kidney from the same donor. Ureteral stenosis developed in both cases. Immunohistochemistry revealed beta 2-microglobulin derived AB amyloid within the stenotic parts of the ureters, which to our knowledge has not been described previously at that site. Usually AB amyloid is found in patients on long-term hemodialysis. Amyloid transfer by transplantation as a possible cause for ureteral stenosis was excluded because the donor had had normal renal function and autopsy showed no evidence of amyloidosis. It is more likely that the secondary deposit of AB amyloid in the transplanted ureters was facilitated by preexisting ischemic ureteral damage.

Amyloidosis↗
PubMed1995

Combined amyloidosis of the upper and lower respiratory tract.

Pulmonary and laryngeal manifestations of localized and organ-limited amyloidosis are sometimes seen, although pulmonary and laryngeotracheal amyloidosis are not always associated. Diagnosis can only be established histologically by the characteristic green birefringence in polarized light after Congo red staining and by immunohistochemical techniques. We describe the case of a 77-year-old woman who presented with hoarseness and an unproductive cough due to extensive amyloid deposits in both the upper and lower respiratory tract, immunohistochemically proven as the A lambda-type.

Aged↗