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Biomedical subjects

M D Benson

Publications and source records attributed to M D Benson.

At least 127 records · Page 7Linked to original sources
PubMed1990

Diagnosis of familial amyloidotic polyneuropathy in France.

Two cases of familial amyloidotic polyneuropathy (FAP) in a French family are reported. Clinical onset was in the fifth and sixth decades with decreased sensation in the lower limbs followed by involvement of the upper extremities. Motor changes appeared later and evolved to restrict ambulation. Cardiac involvement with congestive heart failure and arrhythmias was the cause of death. DNA analysis was performed on ten members of this family. Restriction enzyme analysis of amplification products of exons 2, 3 and 4 of the prealbumin gene were negative for the methionine-30, alanine-60 and serine-84 mutations but positive for the tyrosine-77 mutation. The tyrosine-77 prealbumin mutation was first described in a family from Illinois with origin in Germany. The discovery of the tyrosine-77 gene in the family from Picardy may help to determine the origin of this disease and tell us if one mutation has been spread around the world, as we suspect, with many kindreds having the methionine-30 gene, or whether there have been separate spontaneous mutational events, perhaps a peculiarity of this site in the prealbumin gene.

Aged↗
PubMed1990

A point mutation in transthyretin increases affinity for thyroxine and produces euthyroid hyperthyroxinemia.

In a family expressing euthyroid hyperthyroxinemia, an increased association of plasma thyroxine (T4) with transthyretin (TTR) is transmitted by autosomal dominant inheritance and is secondary to a mutant TTR molecule with increased affinity for T4. Eight individuals spanning three generations exhibited the abnormality. Although five of eight individuals had elevated total T4 concentrations, all affected individuals were clinically euthyroid and all had normal free T4 levels. Purified TTR from the propositus had an affinity for 125I-T4 three times that of control TTR. Exons 2, 3, and 4 (representing greater than 97% of the coding sequence) of the TTR gene of DNA prepared from the propositus' peripheral blood leukocytes were amplified using the polymerase chain reaction (PCR) and were sequenced after subcloning. Exons 2 and 3 were indistinguishable from normal. In 50% of clones amplified from exon 4, a substitution of adenine (ACC) for guanine (GCC) in codon 109 resulted in the replacement of threonine-for-alanine, a mutation confirmed by amino acid sequencing of tryptic peptides derived from purified plasma TTR. The adenine-for-guanine substitution abolishes one of two Fnu 4H I restriction sites in exon 4. PCR amplification of exon 4 of TTR and restriction digestion with Fnu 4H I confirmed that five affected family members with increased binding of 125I-T4 to TTR are heterozygous for the threonine 109 substitution that increases the affinity of this abnormal TTR for T4.

Amino Acid Sequence↗
PubMed1989

Extramedullary plasmacytoma and immunoglobulin-associated amyloidosis in a cat.

Extramedullary plasmacytoma with immunoglobulin-associated amyloidosis was diagnosed in a 10-year-old cat. The primary tumor was a large, circumferential mass of the right tarsal region. Metastasis developed in the regional lymph nodes, spleen, and liver. Permanganate-resistant amyloid deposits were associated with plasma cells in the primary and metastatic tumors. Treatment with prednisone and melphalan had little effect on the progression of the disease, and the cat died four weeks later.

Amyloidosis↗
PubMed1989

Localization of the ankyrin-binding site on erythrocyte membrane protein, band 3.

The predominant attachment site of the spectrin-based cytoskeleton to the erythrocyte membrane occurs via the interaction of ankyrin with the cytoplasmic domain of band 3 (cdb3). In order to further characterize this interaction, we have conducted experiments to localize the ankyrin-binding site on cdb3. Four monoclonal and three antipeptide polyclonal antibodies were raised against cdb3 and used in competition studies to identify regions of close association of cdb3 with ankyrin. Antibodies to regions of cdb3 near the cytoplasmic domain-membrane spanning domain junction had no effect on 125I-ankyrin binding. Likewise, an antibody to a highly conserved region between residues 142 and 154 did not inhibit ankyrin binding. However, antibodies at or near the cysteine 201-317 cluster and the proposed proline-rich hinge in the center of cdb3 were potent inhibitors of ankyrin association, as were antibodies to the acidic NH2 terminus. Additional evidence for interaction of ankyrin with the NH2-terminal region of cdb3 was obtained by demonstrating the ability of ankyrin to inhibit tyrosine phosphorylation of cdb3 at its NH2 terminus by a purified calf thymus tyrosine kinase. These studies reveal two regions of cdb3, distant in primary sequence, which interact with ankyrin. A specific conformation of cdb3 may be required to permit these regions to simultaneously associate with ankyrin and allow binding to occur.

Amino Acid Sequence↗
PubMed1989

Autocrine induction of collagenase by serum amyloid A-like and beta 2-microglobulin-like proteins.

Two autocrine proteins of 14 and 12 kilodaltons that induce the synthesis of rabbit fibroblast collagenase were identified. The proteins were purified from serum-free culture medium taken from rabbit synovial fibroblasts stimulated with phorbol myristate acetate. The amino-terminal sequences of the 14- and 12-kilodalton species were approximately 60 to 80 percent homologous with serum amyloid A and beta 2 microglobulin, respectively. The polyacrylamide gel-eluted proteins retained the ability to induce collagenase synthesis in rabbit and human fibroblasts. These autocrine proteins may provide a means to modulate collagenase synthesis in normal remodeling as well as in inflammation and disease states.

Amino Acid Sequence↗
PubMed1989

Prenatal detection of a gene for hereditary amyloidosis.

Autosomal dominant amyloidosis of the Indiana/Swiss type (familial amyloidotic polyneuropathy type II) is a late-onset disorder characterized by carpal tunnel syndrome, peripheral neuropathy, vitreous opacities, and cardiomyopathy. The genetic basis of the disease is a variant of plasma prealbumin (transthyretin) which has a serine for isoleucine substitution at amino acid 84 of the 127 residue prealbumin molecule. Using the polymerase chain reaction (PCR), we amplified exon 3 of the prealbumin gene in DNA extracted from amniocytes of a fetus at-risk of carrying the serine-84 prealbumin gene. By allele-specific oligonucleotide analysis as well as restriction enzyme analysis of the amplification products it was determined that the fetus was a carrier of the serine-84 variant gene. This finding was confirmed at birth by Southern blot analysis using DNA obtained from cord blood. This is the first report of the prenatal detection of a gene for hereditary amyloidosis.

Amyloidosis↗
PubMed1989

Lack of association of a restriction fragment length polymorphism for serum amyloid P gene with reactive amyloidosis.

The prevalence of a recently described restriction fragment length polymorphism using Msp I for the serum amyloid P gene was determined in 5 groups of patients. Patients with reactive (secondary) amyloidosis, juvenile rheumatoid arthritis, related inflammatory conditions, or juvenile rheumatoid arthritis with reactive amyloidosis, and healthy control subjects were found to be polymorphic for 8.8-kb and 5.6-kb gene fragments; they either had one or the other or both fragments. No significant differences were seen between these groups with relation to this polymorphism, and no correlation with the presence of reactive amyloidosis was observed.

Amyloidosis↗
PubMed1989

Hereditary amyloidosis: evidence against early amyloid deposition.

Twelve members of the Indiana hereditary amyloidosis type II kindred were tested for the presence of amyloid deposits. All were young adults (age 26-37), with no evidence of disease and with 1 affected parent. Six were found to be carriers of the variant gene, by DNA testing and/or reduced serum retinol-binding protein levels. Nevertheless, no amyloid could be found in any skin, rectal, or carpal tunnel biopsy specimens. Our results suggest that hereditary amyloidosis type II is a true late-onset disease, in which accumulation of amyloid does not start until late in life--perhaps only a short time before symptoms appear.

Adult↗
PubMed1989

Familial amyloidotic polyneuropathy.

Amyloidosis has received considerable attention recently because of its association with Alzheimer's disease. Actually, the amyloid in the cortical plaques, which is characteristic of Alzheimer's disease, is a localized form of amyloid deposition. Although intracranial vascular amyloid deposits which contain the A4 or beta-protein are usually associated with Alzheimer's disease, deposition of this amyloid fibril substance in other organs of the body has not been described. Much less attention has been paid to amyloid involvement of the PNS which is a fascinating subject in itself and is the subject of this review.

Amyloidosis↗
PubMed1989

Primary structures of dog and cat amyloid A proteins: comparison to human AA.

1. The complete amino acid sequences of canine and feline amyloid A (AA) proteins were determined and compared with the sequence of human AA protein. 2. The dog and cat AA proteins were 84% homologous with human AA through residue 69. 3. Between the residues which correspond to 69 and 70 in the human sequence, the dog and cat proteins had an insertion of eight amino acids after which homology with human AA resumed. 4. While human AA commonly ends at position 76, the carboxyl termini of dog and cat AA proteins corresponded to position 86 in the sequence of the precursor protein-serum amyloid A. 5. These results are particularly interesting with respect to evolution of the serum amyloid A gene family.

Amino Acid Sequence↗
PubMed1989

Direct sequencing of the gene for Maryland/German familial amyloidotic polyneuropathy type II and genotyping by allele-specific enzymatic amplification.

Direct genomic DNA sequencing has been used to characterize the mutation associated with familial amyloidotic polyneuropathy in the Maryland/German kindred. A mutation of thymine to adenine in the prealbumin (transthyretin) gene at the position corresponding to the second base of codon 58 in the prealbumin mRNA gives a histidine for leucine substitution in the plasma protein. Since the mutation does not result in a change in the restriction pattern of the prealbumin gene, a new method for the direct detection of single base changes in genomic DNA was developed using the polymerase chain reaction and an allele-specific oligonucleotide primer.

Alleles↗
PubMed1989

Amyloidosis related to a lambda IV immunoglobulin light chain protein.

Amyloid subunit proteins related to the lambda IV subgroup of immunoglobulin light chains have not been previously reported. We have determined the amino acid sequence of an AL amyloid protein BAK and shown that it has the structure typical of lambda IV light chain proteins. This protein, which was isolated from the spleen of a patient with AL amyloidosis, has 111 residues in the variable domain and also includes the first tryptic peptide of the constant domain for a total of 130 residues. Comparison of the primary structure of this protein with the only other completely characterized lambda IV protein (SH) reveals that they are highly homologous with only one amino acid change in FR1, two changes in FR2, and one change in FR3. The CDR regions also show few changes, with only three in CDR1, one in CDR2, and five in CDR3. To test the hypothesis that the formation of AL amyloid is related to changes in the FR regions which could affect molecular aggregation, the structure of BAK was compared with the myeloma protein SH with respect to the presumed tertiary structure. Only limited amino acid substitution was found in the surface positions that might affect intradimer and interdimer aggregation. These included an isoleucine for leucine change at position 43 and phenylalanine for valine at 45, which may affect intradimer interaction and a change of histidine to asparagine at position 67.

Amino Acid Sequence↗
PubMed1989

Serum amyloid A protein concentration measured by radial immunodiffusion in Abyssinian and non-Abyssinian cats.

Serum amyloid A (SAA) protein concentration was determined by use of radial immunodiffusion (RID) in 4 groups of cats: Abyssinian cats with amyloidosis, healthy Abyssinian cats without clinical evidence of amyloidosis, hospitalized non-Abyssinian cats, and clinically normal non-Abyssinian cats. Mean SAA concentration in Abyssinian cats with amyloidosis was significantly (P = 0.05) higher than mean SAA concentration in healthy Abyssinian cats without clinical evidence of amyloidosis and in hospitalized non-Abyssinian cats. Mean SAA concentration in clinically normal non-Abyssinian cats was significantly (P = 0.05) lower than mean SAA concentration in healthy Abyssinian cats without clinical evidence of amyloidosis and in hospitalized non-Abyssinian cats. Affected and healthy Abyssinian cats, however, could not reliably be distinguished on the basis of SAA concentration, because of the wide range of SAA values in these 2 groups of cats.

Amyloidosis↗
PubMed1989

Genetic amyloidosis: recent advances.

The hereditary amyloidoses are usually associated with peripheral neuropathy and, for this reason, they have been called familial amyloidotic polyneuropathy (FAP). The neuropathy usually involves both the peripheral sensory motor and autonomic nervous systems, resulting in not only loss of sensation and motor function but also bowel dysfunction and orthostatic hypotension. In addition, most of the FAP syndromes involve other organ systems, in particular the renal and cardiac systems. Renal amyloidosis usually presents as nephrotic syndrome and later terminates in azotemia. Cardiac amyloidosis may present as congestive heart failure or arrhythmia. Whereas the neuropathy of hereditary amyloidosis may be the most prominent clinical feature, it is renal or cardiac disease that often dictates the length of survival.

Alanine↗