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Biomedical subjects

R P Linke

Publications and source records attributed to R P Linke.

At least 19 recordsLinked to original sources
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↗
PubMed1992

Immunohistology of islet amyloid polypeptide in diabetes mellitus: semi-quantitative studies in a post-mortem series.

Immunoreactivity for islet amyloid polypeptide (IAPP) in the islets of Langerhans of non-insulin-dependent diabetic patients and non-diabetic patients of a non-selected post-mortem series was studied with a new polyclonal IAPP antibody. Out of 133 patients examined, 124 exhibited immunoreactivity for IAPP. Immunoreactivity was localized intra- and extracellularly and was limited to the islets of Langerhans. No extracellular immunoreactivity was observed in amyloid-negative cases. Co-localization of insulin and IAPP in the same islet-cells was verified by double staining with monoclonal insulin and polyclonal IAPP antibodies. Of 100 patients with non-insulin-dependent diabetes mellitus (NIDDM) and islet amyloid, 98 exhibited IAPP-positive deposits and 71 exhibited intracellular immunoreactivity. Evaluation of intracellular immunoreactivity and degree of islet amyloid deposition in cases of overt NIDDM revealed an inverse relationship, in that intracellular IAPP immunoreactivity were reduced in patients with developing islet amyloid deposition. Our data are consistent with the hypothesis of primary beta-cell dysfunction leading to amyloid formation, with subsequent disturbance of beta-cell homeostasis.

Aged↗
PubMed1992

Amyloid localized to tenosynovium at carpal tunnel release. Immunohistochemical identification of amyloid type.

Thirty-five patients seen at the Mayo Clinic from 1968 to 1977 who had carpal tunnel syndrome and local deposition of amyloid without evidence of systemic amyloidosis were identified. The unlabeled immunoperoxidase method was used with antisera against purified amyloid proteins of the AA, A kappa, A lambda, AF/ASC1 (prealbumin) (transthyretin), and AB (beta 2-microglobulin) types. In 33 of the 35 patients, amyloid stained with antisera to transthyretin; in the remaining 2 patients, the amyloid did not stain with any antisera. Nine of the 35 patients had a monoclonal protein in the serum, and 2 had a monoclonal light chain in the urine. Systemic amyloidosis or multiple myeloma did not develop in any of these 11 patients. During follow-up, systemic amyloidosis developed in only 2 of the 35 patients: 1 had senile systemic amyloidosis and 1 had tissue that was inadequate for immunohistochemical staining. Amyloid localized to the tenosynovium consists of transthyretin, and systemic amyloidosis rarely develops.

Aged↗
PubMed1992

Immunohistochemical distinction between amyloidosis and fibrillar glomerulopathy.

Six patients with glomerulonephritis and glomerular proteinaceous deposits constituted by fibrillar ultrastructures similar to those of amyloid but lacking the Congo red tinctorial affinity characterizing amyloid were studied. Clinically, these patients had proteinuria and hematuria; in addition, three patients had hypertension and one renal failure. Protein deposits in their kidney biopsy sections were evaluated by immunofluorescence, immunoperoxidase, and immunoelectron microscopic (protein A-gold) techniques, using antibodies against IgG, IgA, IgM, C3, C1q, fibrinogen, immunoglobulin kappa and lambda light chains, and against amyloid fibril proteins of different types, including AA, A lambda, A kappa, and AF. By immunofluorescence and immunoperoxidase, in all cases the deposits stained intensely with antibodies against IgG, C3, and kappa and lambda light chains; one case also showed C1q immunoreactivity. By contrast, none stained with antibodies against various amyloid fibril proteins. Immunoelectron microscopic findings corroborated this data, indicating that the nonamyloid fibrillar deposits studied are antigenically distinct from known amyloid deposits and that they contain IgG-derived material.

Amyloid↗
PubMed1992

Beta-2-microglobulin-derived amyloidosis: onset, distribution and clinical features in 13 hemodialysed patients.

Postmortem examinations were carried out in 13 patients (6 males, 7 females, age 58 +/- 9 years) who had been on regular hemodialysis treatment for 10-90 months using disposable regenerated cellulose membrane dialyzers. The prevalence of beta 2-microglobulin (beta 2m)-derived AB-amyloid deposits in different sites was determined. At autopsy, specimens were obtained from different joints, paravertebral tissue, intervertebral discs and from visceral organs. During life, routine laboratory parameters and radiographic studies had been carried out at 6-month intervals. Serum levels of beta 2m were elevated in all patients (57.5 +/- 13.4 mg/l). Synovial AB-amyloid deposits were shown in different joints of 4 patients, aged between 59 and 73 years, and dialysed for 10-90 months, respectively. All had been unremarkable by X-ray and asymptomatic. No amyloid could be detected in the intervertebral discs of 2 further patients suffering from destructive spondylarthropathy. In 11 of the 13 patients, extracellular beta 2m deposits were observed by immunohistochemistry in different tissues. The results document that (a) AB-amyloidosis may occur in elderly patients even when dialysed for less than 5 years; (b) most cases are completely asymptomatic; the appearance of symptoms must be dependent on additional factors, e.g., site of AB-amyloid deposition and intensity of inflammatory reaction, and (c) AB-amyloid is not the exclusive cause of destructive spondylarthropathy, as 2 typical cases were observed who were devoid of amyloid.

Amyloidosis↗
PubMed1992

Organ-limited laryngeal amyloid deposits: clinical, morphological, and immunohistochemical results of five cases.

Five cases of organ-limited laryngeal amyloid deposits with no evidence of systemic disease are reported in detail and classified immunohistochemically. In four of the five cases the amyloid reacted with anti-A lambda antibodies and in one case with anti-A kappa antibodies. Four of our five female patients had already passed the fifth decade of life. One was 11 years old. Hoarseness was the predominant symptom in four cases, in which we found amyloid deposits in the glottic area. Only one patient, with amyloid deposits in the aryepiglottic fold, complained of pain. The therapy of choice of idiopathic, localized, or organ-limited amyloid deposits without underlying disease may be local excision. In one of the cases reported in this paper, a laryngofissure was performed, and in another a partial laser resection was performed. No therapy was performed in three of our five cases. In the larynx, as in many other locations and only if possible, removal at intervals is more feasible than radical resection, because these amyloid tumors grow slowly.

Amyloidosis↗
PubMed1992

Brain-restricted amyloidoma of immunoglobulin lambda-light chain origin clinically resembling multiple sclerosis.

Cerebral amyloid deposits restricted to the white matter and associated with intracerebral lymphoma were biochemically identified. The patient died at 58 years of age after 37 years of illness with progressive neurological symptoms clinically indicative of multiple sclerosis. Pathomorphologically, spongiform alteration and demyelinization of the white matter in the vicinity of the amyloid deposits was detected and systemic amyloidosis excluded. Immunohistochemically, the amyloid was found to be of immunoglobulin lambda-light chain origin. To establish the nature of this amyloid, its fibrils were extracted and the amyloid fibril proteins isolated by size exclusion chromatography. Immunochemically, the purified amyloid fibril proteins were shown to be of immunoglobulin lambda-light chain origin. This finding was substantiated chemically. Since the N-terminal amino acid was blocked, tryptic peptides were isolated by reversed phase HPLC. The amino-acid sequence of two major peptides revealed homology with the variable region of the immunoglobulin lambda-light chain. This report defines a novel local A lambda-amyloid disease restricted to the white matter of the brain.

Amyloid↗
PubMed1992

Hydrophobic properties of an amyloidogenic kappa I-Bence Jones protein fragment in charge shift electrophoresis.

Increase in hydrophobicity of amyloid-A protein as compared to the serum amyloid-A precursor protein has been demonstrated with charge shift electrophoresis. Charge shift electrophoresis was applied to the kappa-Bence Jones protein MEV, to amyloid-like fibrils generated in vitro by limited proteolysis of MEV and to an isolated, naturally occurring isolated A lambda (ULI) amyloid fibril protein, to see whether an increase in hydrophobicity is also found in to the immunoglobulin-type amyloid. The results also demonstrate here an increase in hydrophobicity during amyloidogenesis of immunoglobulin-derived amyloid fibril proteins, here.

Bence Jones Protein↗
PubMed1991

Inhibition of the oxidative burst response of N-formyl peptide-stimulated neutrophils by serum amyloid-A protein.

Strong binding of the acute phase protein serum amyloid-A (SAA) to human neutrophils was found using flow cytometry. This binding was shown to be functionally relevant with respect to the oxidative burst reaction assayed on N-formyl peptide-stimulated neutrophils by the intracellular oxidation of non-fluorescent dihydrorhodamine to fluorescent rhodamine 123. The results show reduction of the oxidative burst response by isolated SAA (and recombinant SAA2). Inhibition was also demonstrated by acute phase as compared to normal human serum. This inhibitory effect was abolished by the purified monoclonal anti-amyloid A antibody mc29, strongly suggesting that SAA counteracts neutrophil responses to cytokines or bacterial products. This newly recognized function of SAA may help to prevent oxidative tissue destruction.

Adult↗
PubMed1991

Deposition of amyloid of unknown origin in articular cartilage.

Articular cartilage, obtained from the large toe during hallux valgus operations in 37 patients, was investigated for the presence of amyloid by using the Congo red staining method. Amyloid deposits were demonstrated, particularly in the superficial layer of the cartilage, in 30 cases. This amyloid did not react immunohistochemically with any of the antibodies against the known five major amyloid types (AA, A lambda, A kappa, AF, AB). From these data it is concluded that hyaline cartilage in older individuals is prone to infiltration by an amyloid of a hitherto unidentified class. From the morphological observations there seems to be no correlation between amyloid deposits and the development of osteoarthrosis.

Aging↗
PubMed1991

AA-like amyloid deposits confined to arthritic joints in two dogs with rheumatoid arthritis.

Two dogs with clinical, serological, radiographic and pathological changes similar to those of rheumatoid arthritis of man and a previously undescribed pattern of amyloid deposits are described. As revealed by light and electron microscopical investigations, amyloid fibrils were found exclusively in articular tissue structures of arthritic joints and in one tonsil of one dog. Based on our immunohistochemical results, the amyloid protein is believed to be of a local AA type.

Animals↗
PubMed1991

Unilateral extended amyloidosis of the renal pelvis and ureter: a case report.

Localized amyloidosis of the genitourinary tract is a rare phenomenon. The differential diagnosis between amyloidosis and malignancy is difficult. We report the case of an 81-year-old man with extensive unilateral localized amyloidosis of the renal pelvis, ureter and ureteral orifice. Diagnosis of amyloidosis was confirmed only postoperatively.

Aged↗
PubMed1991

Equine cutaneous amyloidosis derived from an immunoglobulin lambda-light chain. Immunohistochemical, immunochemical and chemical results.

Amyloid deposits from equine cutaneous nodular amyloidosis associated with extramedullary plasmacytoma were classified immunohistochemically as equine immunoglobulin lambda-light chain-derived and designated eA lambda (HIP). For chemical identification, the amyloid fibril proteins were separated on Sephadex G-100 in 6M guanidine.HCl. Polypeptides of predominantly 24 kDa and 50 kDa were found by polyacrylamide gel electrophoresis. They have preponderance of immunoglobulin lambda-antigenic determinants as detected by immunodiffusion and immunoblotting. Since the N-terminus of the major proteins was blocked, peptides were generated with trypsin and endoproteinase Asp-N and then isolated using reversed-phase high-performance liquid chromatography. Automatic amino-acid sequence determination of seven peptides showed novel sequences. Data bank comparison indicated that these peptides were derived from a monoclonal immunoglobulin lambda-light and a gamma-heavy chain. The light chain was considered to be the leading amyloidogenic polypeptide, since it was the predominant component in a virtually pure amyloid fibril preparation. Thus, immunoglobulin lambda-light chain-derived amyloidosis, so far established only in man and cat, has now also been identified in the horse.

Amino Acid Sequence↗
PubMed1990

High molecular weight kininogen-binding site of prekallikrein probed by monoclonal antibodies.

A panel of monoclonal antibodies against human prekallikrein was raised in mice and characterized with respect to the major antigenic epitopes. Of 18 antibodies, nine were directed against the light chain portion performing the proteolytic function of activated kallikrein, and nine recognized the heavy chain mediating the binding of prekallikrein to high molecular weight (H-)kininogen. Among the anti-heavy chain antibodies, one (PK6) interfered with the procoagulant activity of prekallikrein, and prolonged in a concentration-dependent manner the activated partial thromboplastin time of reconstituted prekallikrein-deficient plasma (Fletcher type). Antibody PK6 was subtyped IgG1,k and had an apparent Kass of 6.8 +/- 0.44.10(8) M-1 for prekallikrein. Functional analyses revealed that PK6 does not interfere with prekallikrein activation by activated Hageman factor (beta-F XIIa), and has no effect on the kininogenase function of activated kallikrein. Monoclonal antibody PK6 but none of the other anti-heavy chain antibodies completely prevented complex formation of prekallikrein with H-kininogen, and readily dissociated preformed complexes of prekallikrein and H-kininogen. Likewise, Fab' and F(ab')2 fragments of PK6 blocked H-kininogen binding to prekallikrein. A synthetic peptide of 31 amino acid residues encompassing the entire prekallikrein binding region of H-kininogen effectively competed with PK6 for prekallikrein binding indicating that the target epitope of PK6 is juxtaposed to, if not incorporated in the H-kininogen-binding site of prekallikrein. Extensive cross-reactivity of PK6 with another H-kininogen-binding protein of human plasma, i.e. factor XI, suggested that the structure of the target epitope of PK6 is well conserved among prekallikrein and factor XI, as would be expected for the kininogen-binding site shared by the two proteins. It is anticipated that monoclonal antibody PK6 will be an important tool for the precise mapping of the hitherto unknown kininogen-binding site of prekallikrein.

Antibodies, Monoclonal↗
PubMed1990

Heterogeneity of human serum amyloid A protein. Five different variants from one individual demonstrated by cDNA sequence analysis.

Serum amyloid A (SAA), a chemically polymorphic protein, is the most sensitive marker protein of the acute phase and the precursor of reactive amyloidosis, which is characterized by deposits of amyloid A protein (AA). We investigated the variability of the SAA gene family in one individual by sequencing 11 SAA-specific clones from an acute-phase-liver cDNA library. At least five different SAA variants were deduced from six different cDNAs. The 3' untranslated gene segments fall into two groups, based on nucleotide sequence and variability in length. Various nucleotide and amino acid substitutions were found predominantly in the 3' portion. Some of these substitutions are unique and increase the number of SAA variants in one individual to at least five. Moreover, genomic DNA of four individuals was examined by analysis of restriction-fragment length polymorphism. Besides two conserved strongly labelled bands, additional polymorphic bands were observed, indicating isotypic and/or allotypic SAA variations. Finally, three different mRNA species were detected by Northern-blot analysis, a finding that might be of relevance for the stability of SAA transcripts.

Amino Acid Sequence↗
PubMed1990

Amyloid in intervertebral discs of surgery and autopsy material. A new class of amyloid?

Intervertebral discs from 82 consecutive operations on herniation and 59 autopsies (one case with generalized amyloidosis) were studied. Amyloid deposits observed in surgical and autopsy specimens increased with age in both series. Degenerative changes were related to age and to amyloid deposits in autopsy, but not in surgical cases. Calcium pyrophosphate dihydrate deposits (often in proximity to amyloid deposits) were found in autopsy discs of six patients and in surgical specimens of three patients with previous operations on herniated discs. Antisera against amyloid fibril proteins of different types including AA-, A lambda-, A kappa, AF- and AB-types showed no reaction with disc amyloid. In one case with generalized A lambda-amyloidosis the disc amyloid was not of the A lambda-type. Based on our results, we suppose that disc amyloid is a form of localized senile amyloidosis - possibly representing a new class of amyloid limited to cartilage tissue.

Adult↗