Showing papers by "Martha Skinner published in 1991"

Proline at position 36: a new transthyretin mutation associated with familial amyloidotic polyneuropathy.

Abstract: Familial amyloidotic polyneuropathy (FAP) is associated with the deposition of an abnormal transthyretin (TTR) molecule. We have studied DNA from a family of Greek descent with FAP. The proband's TTR gene was asymmetrically amplified by using PCR and then was sequenced directly, to reveal a cytosine-for-guanine substitution in codon 36. This substitution removes a recognition site for endonuclease Fnu4HI. Allele-specific PCR was employed for diagnosis of the mutation. The predicted amino acid change of alanine to proline at position 36 was confirmed by protein sequencing of the proband's plasma TTR.

The predictive value of bone marrow morphologic characteristics and immunostaining in primary (AL) amyloidosis.

Abstract: The authors previously demonstrated that bone marrow plasmacytosis in primary (AL) amyloidosis may be monoclonal or polyclonal. However, the clinical implications of the degree of plasmacytosis and its clonality have not been studied. The authors evaluated 62 patients with AL amyloidosis, 40 of whom had monoclonal medullary plasma cells. There was complete concordance between the light chain class of the plasma cells in the monoclonal cases and that of the circulating paraprotein in the 22 cases associated with a paraprotein. The remaining 22 patients had polyclonal plasma cells, although a paraprotein was detected in 6. The degree of plasmacytosis was significantly higher among patients with monoclonal plasma cells and correlated inversely with length of survival. The authors' findings indicate that the quantitation of bone marrow plasma cells in AL amyloidosis by immunoperoxidase studies may predict the clinical course.

New USA Family has Apolipoprotein AI (ARG26) Variant

Abstract: We have studied a patient from Massachusetts with hereditary systemic amyloidosis significant for renal dysfunction and liver infiltration culminating in hepatic failure and death at the age of 43 years, with no history of peptic ulcer disease or peripheral neuropathy. Amyloid fibrils isolated from this patient were fractionated and the 11 KD product found in the major retarded protein peak was sequenced to reveal a homogeneous apo A-l variant with arginine for glycine at position 26. This same mutation has been reported in a family from Iowa with a type-III FAP and a 9 KD fragment of a variant apolipoprotein A-1 as the major protein in their amyloid deposits. Peripheral neuropathy and peptic ulcer disease were the prominent symptoms in the Iowan family. The differences between the clinical descriptions of the two kindreds suggest that the apo A-l mutation of arg26 may have a variety of manifestations.

Long Survival in Patients with Al Amyloidosis

Abstract: Eighteen of 127 patients with AL amyloidosis seen before October 1984 were found to have survived 60 months or longer. For this study, a control patient matched for the nearest date of diagnosis was analyzed with each long survivor. Six male and 12 female patients comprised the long survivor group, compared to 10 males and 8 females in the control group. Median survival from diagnosis was 93.3 months (range 60.9-205.3) for the long survivors and 12.3 months (2.3-56.5) for the controls. The marked difference in survival could not be predicted by organ system involvement.

ASN 90 is the Variant TTR in an Italian FAP Kinship

Abstract: A new transthyretin variant which lost an Sph I cleavage site within exon 3 has been characterized. A 260bp sequence containing exon 3 was amplified using the polymerase chain rection, and the variant was found to possess a Bsm I cleavage site not present in normal transthyretin. This led to the conclusion that the histidine at position 90 was replaced by asparagine, and amino acid analysis supported the conclusion.

Secondary Structure Changes in Mutant Transthyretins after Proteolysis by Neutrophilic Serine Proteases

Abstract: The secondary structure of plasma transthyretin (TTR) from patients with familial amyloidotic polyneuropathy was studied with respect to alteration in the amount of beta conformation after exposure to proteolytic enzymes of the neutrophilic serine protease family. We examined TTR from four affected individuals, each with a different mutation or at a different stage of disease. After exposure to human neutrophilic elastase (HNE) or cathepsin G, circular dichroic (CD) spectra for each was compared to normal.

First Turkish Family with FAP has Homozygous Met 30 TTR

Abstract: The first family of Turkish origin with typical familial amyloidotic polyneuropathy type I was studied. Two symptomatic brothers were found to be homozygous for the met 30 mutation of transthyretin (TTR) by examination of their TTR genes using polymerase chain reaction. Both brothers developed symptoms in the sixth decade of life and no family history of FAP was present.

Quantification of Amyloid P-Component in Multiple Tissues of Patients with Primary and Familial Amyloidois

Abstract: Amyloid P component (AP) is a constitutive plasma protein that has been closely linked to deposits of amyloid fibrils. This study examines the amount of AP in three tissues (spleen, liver and heart) of two patients, one with primary (AL) and one with familial (ATtr) amyloidosis. AP was found in all three tissues of both patients. This is the first time it has been quantified in amyloidotic cardiac tissues of any type. The amount of AP in the ATtr heart equaled or exceeded the amounts in the AL heart. The consistently large amount of AP associated with all tissues of all types of amyloidosis may provide a clue to pathogenetic mechanisms involved in light chain and transthyretin (Ttr) fibrillogenesis.

Cardiac Involvement in Secondary Amyloidosis

Abstract: Cardiac symptoms are reported to occur rarely in patients with secondary (AA) amyloidosis (1), and while autopsy data have indicated that cardiac amyloid deposits occur in up to 25% of patients, the cause of death is not usually felt to be related to cardiac disease (2). Although a number of reports have documented the diagnostic utility of echocardiography in primary amyloidosis, there is little information regarding the echocardiographic and clinical cardiac features of patients with secondary amyloidosis. We sought to better characterize the clinical, electrocardiographic and echocardiographic features of secondary amyloidosis in a retrospective review of consecutive patients evaluated at the Thorndike Memorial Laboratory of Boston City Hospital.

Patients with primary and familial amyloidois

Abstract: Amyloid P component (AP) is a constitutive plasma protein that has been closely linked to deposits of amyloid fibrils. This study examines the amount of AP in three tissues (spleen, liver and heart) of two patients, one with primary (AL) and one with familial (ATtr) amyloidosis. AP was found in all three tissues of both patients. This is the first time it has been quantified in amyloidotic cardiac tissues of any type. The amount of AP in the ATtr heart equaled or exceeded the amounts in the AL heart. The consistently large amount of AP associated with all tissues of all types of amyloidosis may provide a clue to pathogenetic mechanisms involved in light chain and transthyretin (Ttr) fibrillogenesis.