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R P Linke

Publications and source records attributed to R P Linke.

At least 55 records · Page 3Linked to original sources
PubMed1995

High-sensitivity diagnosis of AA amyloidosis using Congo red and immunohistochemistry detects missed amyloid deposits.

Biopsy diagnosis of early amyloid-A (AA) amyloidosis has often been difficult. Examination of 57 consecutive biopsy specimens from 42 patients with inflammatory pediatric diseases permitted comparison of the precision of biopsy amyloid diagnosis in six different laboratories (labs), which applied the following methods: Congo red alone (four unspecialized labs combined as Lab 1), Congo red and electron microscopy (Lab 2), or Congo red and immunohistochemistry using monoclonal antibodies (Lab 3). Lab 3 reexamined the diagnoses made by Lab 1 and Lab 2. Of the 42 patients, 17 patients with 32 biopsies were selected for this study based on the presence of amyloid in at least one biopsy. Whereas massive or no amyloid was concordantly recognized by all labs in 18 biopsies from nine patients, discordance was demonstrated in 14 biopsies from eight patients. Comparison of Labs 1-3 revealed amyloid in 12 rectal and 18 renal biopsies evaluated by Lab 3, whereas Lab 2 missed amyloid in two of 18 renal biopsies and Lab 1 missed amyloid in 11 of 12 rectal biopsies. Most amyloid was missed when only minute amounts of amyloid were present. Had our technique (Lab 3) been available at the time of biopsy, amyloid could have been diagnosed years earlier, thereby sparing the patient further biopsies and allowing initiation of earlier treatment before organ damage could occur.

Adolescent↗
PubMed1995

Interstitial amyloid deposits in the pituitary gland. Morphometry, immunohistology, and correlation to diseases.

The prevalence and immunoreactivity of interstitial amyloid deposits of the pituitary glands of 109 consecutive autopsies of individuals over 84 years of age were studied using Congo red staining and antibodies directed against the major amyloid fibril proteins and pituitary hormones. In addition, the amount of interstitial amyloid formation was evaluated quantitatively and compared with all autopsy-related and clinical diagnoses available. Eighty-seven (80%) of the 109 cases exhibited interstitial amyloid deposits in the anterior lobe. All reacted immunohistochemically with antiamyloid lambda light chain and antiamyloid P-component. Quantitative analysis in 62 cases revealed a mean volume percentage of interstitial amyloid in the anterior lobe of 0.56%. In statistical analysis, only two of the 25 diseases recorded were associated with interstitial amyloid: chronic obstructive pulmonary disease and non-insulin-dependent diabetes mellitus. The prevalence of chronic obstructive pulmonary disease correlated positively with the occurrence (chi 2; P < .02) as well as with the amount of amyloid (Wilcoxon; P < .04) in the pituitary. In addition, non-insulin-dependent diabetes mellitus was accompanied with higher amounts of interstitial amyloid than with all other disorders (Wilcoxon; P < .03). Until now, a correlation was proposed only between non-insulin-dependent diabetes mellitus and islet amyloidosis of the pancreas.

Aged↗
PubMed1994

[Fatal generalized AA amyloidosis in mutilating psoriatic arthropathy].

Autopsy findings are reported of a 51-year-old female patient with a 40-year history of mutilating psoriatic arthritis. As a result of this disease the patient developed reactive amyloidosis (AA-type) with generalized vascular involvement, amyloid kidneys and unusual amyloid goitre. The cause of death was ischaemic left ventricular failure due to massive amyloid deposits in the coronary arteries and left ventricular hypertrophy, the latter resulting from renal hypertension. Thus, amyloidosis and ischaemic heart disease were late complications of the underlying inflammatory disease.

Amyloidosis↗
PubMed1994

Gastrointestinal amyloid deposits in old age. Report on 110 consecutive autopsical patients and 98 retrospective bioptic specimens.

The prevalence of gastrointestinal amyloid was determined in 110 consecutive autopsy patients aged 85 years and older. Paraffin sections from the esophagus, stomach, small intestine, colon and rectum were stained with Congo red and inspected in polarized light. Amyloid was found in 38 patients (36%). Four patients had generalized amyloidosis and the remaining 34 revealed more localized varieties of amyloid. Immunohistochemical classification with a panel of antisera directed against five major amyloid fibril proteins displayed at least four different types of amyloid. Twenty cases exhibited amyloid of transthyretin origin, five cases were of lambda light chain origin and one case was of amyloid A-type. Thus far, unclassifiable amyloid deposits were found in 18 cases, 16 of which were strictly localized in subserosal veins. This consecutive autopsy series was compared with 98 randomly-selected bioptical gastrointestinal tissues with amyloid according to distribution pattern, sex, frequency of the various types of amyloid and associated diseases.

Aged↗
PubMed1994

Light microscopic, ultrastructural, and immunohistochemical examinations of two calcifying epithelial odontogenic tumors (CEOT) in a dog and a cat.

Two calcifying epithelial odontogenic tumors from a 10-year-old cross-breed dog and a 9-year-old cat were characterized histologically and electron microscopically. Important characteristics were plexiform to squamous epithelial structure, amyloid in the tumor tissue with partial calcification (Liesegang's rings), and a low rate of mitosis. The amyloid found in the tumors was subjected to immunohistochemical examination, using a series of antibodies (anti-AA, -AL, -AF, -ASc1, -AB, -cytokeratin, -vimentin, -desmin, -laminin). The exclusive reaction to anti-cytokeratin and anti-laminin suggests that the amyloid is of epithelial origin.

Amyloid↗
PubMed1993

[Whipple's disease with reactive (AA) amyloidosis].

A 59-year-old man had been known for two years to have a clearly elevated blood sedimentation reaction and intermittent arthralgia in the hand. His general condition had progressively deteriorated over the last six months, with weight loss, recurrent vomiting and constipation. At first malignant lymphoma had been suspected because numerous lymph nodes were enlarged. But a lymph-node biopsy revealed massive macrophages with PAS-positive inclusion material, diagnosed as Whipple's disease. The patient died suddenly of a heart attack on the day of diagnosis. At necropsy generalized amyloidosis with marked cardiac involvement was found. Immunohistochemically the amyloid deposits gave a strongly positive reaction to anti-AA, while other amyloid syndromes were excluded using appropriate anti-sera. This was therefore a case of reactive (AA) amyloidosis in the presence of Whipple's disease.

Amyloidosis↗
PubMed1993

The precursor molecule of a V lambda II-immunoglobulin light chain-derived amyloid fibril protein circulates precleaved.

The putative precursor molecule of a human AL type amyloid fibril protein was isolated from an ultrafiltrate after hemofiltration. Subsequent separation of this protein was achieved by high performance liquid chromatography (HPLC) after reduction and carboxymethylation of the disulfide bonds. The protein was separated into several fractions which were further analyzed by automatic amino acid sequence determination. It was deduced from the sequence data that the precursor molecule is an immunoglobulin L-chain of the lambda-type. The V-region of this protein is most closely related to the proteins of subgroup II. Internal splits occurred in the molecule after lysine residues in positions 110, 129 and 179. The predominant fragment commences with either serine or alanine in position 9 and extends to a serine in position 65 of the V-region. Tryptic peptides generated from the fragments cover nearly the entire V- and C-region of the L-chain, with the exception of positions 1-8, from which no peptide has been isolated.

Amino Acid Sequence↗
PubMed1993

Cardiac amyloidosis: a review and report of a new transthyretin (prealbumin) variant.

Cardiac amyloidosis is caused by amyloid deposits derived from different human plasma proteins. It can lead to cardiac conduction disturbances, restrictive cardiomyopathy, and low output heart failure. The heart is variably involved during the development of systemic amyloidosis and seems to be more frequently affected in immunoglobulin (primary) than in reactive (secondary) amyloidosis. Amyloid is common in the elderly. Isolated atrial amyloid, for which a major subunit is the atrial natriuretic peptide, seems to be three times more frequent than senile cardiac amyloid, which is derived from normal prealbumin (transthyretin). Like polyneuropathy, cardiac amyloidosis is a prominent clinical feature of hereditary amyloidosis, namely of the autosomal dominant transthyretin (TTR) type. All 28 cases of TTR amyloidoses reported so far were heterozygotes for a single nucleotide change in the gene for TTR that resulted in amino acid substitutions in the mature protein. A new TTR genetic variant is reported in a German family where the index patient presented at the age of 63 with anginal pain and arrhythmia. Electrocardiography was suggestive of a pseudoinfarction pattern, and echocardiography and cardiac catheterisation showed signs of hypertrophic nonobstructive cardiomyopathy with increased ventricular filling pressures and a prominent "a" wave. Amyloid of the TTR type was identified by immunohistochemistry in the endomyocardial biopsy specimen. Hybrid isoelectric focusing established heterozygosity by showing normal TTR protein and an electrically neutral TTR variant differing from all known TTR variants so far. The patient died in an accident before investigations were complete. Electrophoretic analysis of the plasma from his first degree relatives (son, daughter, brother, and mother) identified the asymptomatic 22 year old son as an apparently heterozygous carrier of the mutant TTR protein. Comparative tryptic peptide mapping and sequencing showed that isoleucine at position 68 of the amino acid sequence was replaced by leucine.

Amino Acid Sequence↗
PubMed1993

Therapy of amyloid diseases.

Deposition of amyloid in the organism can lead to severe clinical symptoms and syndromes which are referred to as amyloidosis. However, amyloidosis is not a pathogenetically single disease entity. Various amyloid diseases are known which can clearly be distinguished by identifying the protein from which the amyloid is derived. Since the amyloid syndromes are pathogenetically diverse, each of the different amyloid diseases needs to be treated differently, and a type-specific amyloid therapy is mandatory. Unfortunately, an efficient therapy is not yet available for most amyloid syndromes. It is the purpose of this review to show how the different amyloid syndromes are distinguished definitively from each other and what has been successful in the effort to establish an efficient therapy of the various amyloid deposits and different amyloidoses.

Amyloidosis↗
PubMed1993

Cerebral amyloid angiopathy. Frequency, significance and immunohistochemistry.

For the assessment of the anatomical distribution of cerebral amyloid angiopathy (CAA) as well as that of amyloid plaques (AP), 955 post-mortem brain specimens from 653 patients (aged 14 to 95 years) were made available from a general hospital. Using histological and immunohistochemical techniques, we demonstrated amyloid angiopathy chiefly in the occipital, parietal and temporal regions. Senile plaques were mostly found in parietal, temporal and occipital areas. In our cases, neurofibrillary tangles were rarely prominent in the regions examined. There was often a significant difference in the frequency of amyloid angiopathy and of plaques in distinct areas between men and women. Congophilic angiopathy was associated with senile plaques in 82.3%, and neurofibrillary tangles with plaques in 76.9%. In comparison, the correlation of amyloid plaques with CAA (32.5%) and of plaques with neurofibrillary tangles (11.5%) was less pronounced. There was a strong association of cerebral vascular amyloid with age in both sexes, it was more pronounced in women than in men. Unexpectedly, CAA showed a decrease in frequency in men in the 7th and 8th decade of life. In addition, there was a positive correlation between the amount of CAA and spontaneous hemorrhages, but no correlation with ischemic encephalopathy. Immunohistochemistry showed that cerebral amyloid was neither amyloid of the AA- nor of the ATTR-(Antitransthyretin-, formerly anti-AF)-type. An antibody to the beta-protein (anti-A beta) showed cerebral vascular deposits to be congruent with the Congo red method, whereas senile plaques stained weakly and neurofibrillary tangles could not be stained at all with these antibodies.

Adolescent↗
PubMed1993

[Amyloidosis cutis nodularis atrophicans (Gottron)].

We report an exceptionally severe case of amyloidosis cutis nodularis atrophicans (Gottron) of the lower limbs in a 49-year-old female patient. The diagnosis was made on clinical and histological grounds and was confirmed by immunohistochemical evidence of amyloid of the A-lambda type. For the first time, cutaneous microcirculation in the region of the nodules was investigated by means of fluorescence video microscopy. Pronounced microangiopathy characterized by avascular fields, enlarged and tortuous capillaries and increased transcapillary diffusion of sodium fluorescein, was clearly demonstrable in the area of the nodules. The pathogenetic role of these vascular changes is discussed.

Amyloid↗
PubMed1993

Hemodialysis: demonstration of truncated beta 2-microglobulin in AB-amyloid in situ.

Amyloid deposits of patients on long-term hemodialysis consist of a considerable proportion of beta 2-microglobulin (beta 2m) fragments, as demonstrated by N-terminal amino acid sequence analysis of isolated amyloid fibril proteins. Since this finding may have pathogenetic relevance, we have produced fragment-specific antibodies directed against a synthetic peptide of beta 2m (P132) commencing at position 20. Absorption of this antiserum on insolubilized beta 2m and subsequent isolation of the anti-P132 antibody from the insolubilized P132 peptide yielded a cleavage site-specific antibody which reacted only with P132, but not with a control fragment of beta 2m and only marginally with a beta 2m preparation in micro-ELISA. When applied onto tissue sections from various organs with AB-amyloid using an immunoperoxidase method, the fragment-specific anti-P132 antibody reacted immunohistochemically predominantly with renal AB-amyloid stones, but not with all amyloid from large joints and bone marrow amyloid-tumors, in contrast to an anti-AB or beta 2m-antibodies, which intensely stained all deposits. Thus, the presence of fragmented beta 2m-molecules have been demonstrated in amyloid in tissue sections. These data are in accordance with the results of chemical studies.

Adult↗
PubMed1993

Fibrillar protein deposits with tubular substructure in a systemic disease beginning as cutis laxa.

BACKGROUND: The homogeneous material found in the skin is commonly identified as amyloid. We describe a previously unknown disease that is caused by proteinaceous deposits and that does not fulfill the criteria of the earlier recognized amyloid diseases. OBSERVATIONS: The unusual deposits, which were initially found in the dermis, were ultrastructurally composed of fibrillar material with a tubular substructure. Immunohistologically, the material was tested using a large panel of antibodies, and the results revealed that it was unlike any commonly known proteinaceous material. The deposits later spread to other organs and disturbed the vital functions of the body. CONCLUSIONS: We describe a unique syndrome characterized by fibrillar extracellular deposits that was recognized and differentiated from other similar clinical syndromes by ultrastructural examination. Further biochemical analysis is necessary to identify the origin of the material.

Cutis Laxa↗
PubMed1992

Incidence and natural history of primary systemic amyloidosis in Olmsted County, Minnesota, 1950 through 1989.

No reports of the incidence rates for primary systemic amyloidosis (AL) have come to our attention. Records of all residents of Olmstead County, Minnesota, with a diagnosis of amyloidosis were obtained from the Mayo Clinic and its affiliated hospitals, as well as other medical groups that might have seen local patients for the period January 1, 1950 to December 31, 1989. Twenty-one patients fulfilled the criteria for the diagnosis of AL. The median age was 73.5 years, and 62% were men. In all but one patient the diagnosis was made ante mortem. The clinical data of the 21 patients were similar to those referral patients with AL seen at Mayo Clinic. Immunohistochemical stains were positive for monoclonal light chains in the amyloid deposits in 15 of the 21 cases. In six cases, tissue was not available for immunohistochemical studies. Three of the six patients without immunohistochemical stains had a free monoclonal lambda light chain in the urine, and the other three had a monoclonal serum protein. Immunoelectrophoresis/immunofixation detected a monoclonal (M)-protein in the serum of 16 of 17 patients tested. A monoclonal light chain was found in the urine of 10 of 15 patients. The overall sex- and age-adjusted rate per million person-years was 6.1 from 1950 to 1969 and 10.5 from 1970 to 1989. The similarity of these rates suggests no significant increase over time.

Aged↗
PubMed1992

AL amyloidosis mimicking a preferentially autonomic chronic Guillain-Barré syndrome.

We report a case history of a patient whose diagnosis of AL amyloidosis remained elusive until postmortem examination. Exhaustive autonomic neuropathy mimicking a chronic Guillain-Barré syndrome dominated the clinical picture. The problems in establishing the definitive diagnosis of AL amyloidosis even in the face of strong clinical evidence are discussed.

Amyloid↗