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Biomedical subjects

M D Benson

Publications and source records attributed to M D Benson.

At least 145 records · Page 8Linked to original sources
PubMed1989

Spinal claudication in systemic amyloidosis.

We describe a patient with hereditary amyloidosis who developed the syndrome of spinal claudication. Myelography and computerized tomography of the lumbar spine demonstrated stenosis of the spinal canal and surgical exploration confirmed dense amyloid infiltration of ligamentous structures compressing the nerve roots. Two cousins of our patient and 2 patients with immunoglobulin amyloidosis had similar clinical syndromes. Spinal stenosis can be demonstrated by myelography or by computerized tomography. Diagnosis of this syndrome is important since wide decompression may be needed to relieve symptoms. Patients who had only disc extraction did not improve after the operation; their symptoms persisted and even worsened.

Amyloidosis↗
PubMed1989

A unique insertion in the primary structure of bovine amyloid AA protein.

Amyloid fibrils were isolated from kidney tissue of a cow afflicted with renal failure caused by spontaneous reactive amyloidosis. These fibrils were reduced and alkylated, and the amyloid subunit protein was isolated on a column of Sepharose CL6B. The protein was fragmented with both trypsin and Staphylococcus protease, and the resultant peptides were separated by high-performance liquid chromatography. Sequence analysis gave the complete primary structure of the protein with overlaps of the tryptic peptides confirmed by the Staphylococcus protease peptides. Comparison of the bovine amyloid A (AA) amino acid sequence with human protein AA demonstrates complete invariability from human position 33 to 45 and a very high degree of homology from positions 16 to 29 and 46 to 63. These data indicate that these portions of the molecule may be significant factors in amyloid fibrilogenesis. The bovine AA protein shows a blocked amino terminus, as is the case with the dog and the cat AA proteins. In addition, this protein contains an insertion of nine amino acid residues between human positions 69 and 70. The existence of an additional six residues after position 76 makes the bovine AA an unusually large 90 amino acid peptide. These findings point to a high tolerance for mutation in the carboxyl end of the molecule.

Amino Acid Sequence↗
PubMed1988

Variant apolipoprotein AI as a major constituent of a human hereditary amyloid.

Amyloid fibrils were isolated from spleen and liver of a patient who died with Familial Amyloidotic Polyneuropathy Type III (Iowa). The major protein constituent of the fibrils was found to be the amino terminal portion (residues 1-83) of apolipoprotein AI with an arginine for glycine substitution at position 26. This is the first report of an apolipoprotein as a major amyloid constituent in a form of autosomal dominant hereditary amyloidosis in humans.

Amino Acid Sequence↗
PubMed1988

Amino acid structures of multiple forms of amyloid-related serum protein SAA from a single individual.

Multiple forms of the acute-phase serum protein SAA were isolated from the lipoprotein fraction of plasma from a single individual. These protein forms were purified by size-exclusion, ion-exchange, and reverse-phase high-pressure liquid chromatography, and then the tryptic peptides were subjected to amino acid sequence analysis. A total of three distinct 104-residue proteins were identified. Two of these proteins differed only by having either an arginine or a histidine at position 71 while the third protein had seven amino acid differences. Each of these proteins has a 103-residue companion protein where the amino-terminal arginine has been removed. Two of these protein sequences match the two human SAA cDNA structures reported in the literature. The presence of three unique amino acid sequences in one individual is proof that there must be a minimum of two genes for SAA in humans.

Aged↗
PubMed1988

Identification of a new hereditary amyloidosis prealbumin variant, Tyr-77, and detection of the gene by DNA analysis.

In the last several years, five human plasma prealbumin (transthyretin) variants have been discovered in association with hereditary amyloidosis, a late-onset fatal disorder. We recently studied a patient of German descent with peripheral neuropathy and bowel dysfunction. Biopsied rectal tissue contained amyloid that stained with anti-human prealbumin. Amino acid sequence analysis of the patient's plasma prealbumin revealed both normal and variant prealbumin molecules, with the variant containing a tyrosine at position 77 instead of serine. We predicted a single nucleotide change in codon 77 of the variant prealbumin gene, which we then detected in the patient's DNA using the restriction enzyme SspI and a specifically tailored genomic prealbumin probe. DNA tests of other family members identified several gene carriers. This is the sixth prealbumin variant implicated in amyloidosis, and adds to the accumulating evidence that the prealbumin amyloidoses are more varied and prevalent than previously thought.

Amyloidosis↗
PubMed1988

Human serum amyloid A. Three hepatic mRNAs and the corresponding proteins in one person.

Serum amyloid A protein (SAA) is a major acute-phase protein in humans and most other mammals. In addition, it is the serum precursor of the major protein constituent of reactive amyloid fibrils. Sequence analyses have identified a number of polymorphic forms of human SAA and amyloid A protein (AA), but the question of the number of genes encoding SAA in the human has not been addressed. In addition, there are insufficient data to predict whether one form of SAA predisposes to amyloid fibril formation. In the present study three separate SAA proteins have been isolated from the plasma of one individual and completely sequenced. While two of the SAA forms (SAA2 alpha and SAA2 beta) differ from each other only at position 71, they differ from the most abundant form (SAA1) at seven and eight other positions, respectively. Nucleotide sequencing of cDNAs from a liver library of this individual identified all three mRNs coding for these proteins and proved that: (a) the often-reported absence of arginine at the amino terminus of SAA proteins must result from proteolytic processing of the protein; (b) the polymorphism involving histidine and arginine at position 71 is present at the DNA level and therefore is not due to an event at the translational level; (c) there are at least two genes coding for human SAA. Comparison of these data to published sequences of SAA and AA proteins may help in identifying genetically determined forms of SAA which predispose to reactive amyloid fibril formation.

Amino Acid Sequence↗
PubMed1988

A DNA test for Indiana/Swiss hereditary amyloidosis (FAP II).

Autosomal dominant amyloidosis of the Indiana/Swiss type is a late-onset disorder characterized by carpal tunnel syndrome, progressive peripheral neuropathy, vitreous deposits, and cardiomyopathy. This disorder was originally described in a large Indiana family of Swiss descent and is also known as familial amyloidotic polyneuropathy (FAP) type II. In the Indiana family, 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. We predicted that the corresponding mutation in the prealbumin gene consisted of a T-to-G change in codon 84 (which created an AluI recognition site) and then demonstrated the extra AluI site in the DNA of patients by Southern blot analysis with a genomic prealbumin probe. This verifies the protein findings at the DNA level and provides a direct, reliable DNA test for the Ser-84 prealbumin gene associated with Indiana/Swiss hereditary amyloidosis.

Amyloidosis↗
PubMed1987

Hereditary amyloidosis: description of a new American kindred with late onset cardiomyopathy. Appalachian amyloid.

A family with hereditary amyloidosis characterized by peripheral neuropathy and cardiomyopathy is described. Lack of eye involvement sets their disease apart from the Indiana/Swiss familial amyloidotic polyneuropathy type II. The disease is of late onset; affected members die of cardiomyopathy after age 60. The late onset and lack of clinically significant neuropathy in several family members has led to misdiagnosis of the cardiomyopathy. Immunohistochemistry using antiprealbumin antiserum showed staining of amyloid deposits in nerve and heart.

Adult↗
PubMed1987

Primary structure of amyloid fibril protein AA in azocasein-induced amyloidosis of CBA/J mice.

Secondary amyloidosis was induced in CBA/J mice by subcutaneous injections of azocasein after priming with amyloid-enhancing factor. Amyloid fibrils were isolated from spleens and the subunit amyloid A (AA) protein purified by gel filtration on a column of Sepharose CL6B. The AA protein was fragmented with trypsin, cyanogen bromide, and Staphylococcus protease, and the peptides were purified by reverse-phase high-performance liquid chromatography. This protein is composed of 73 amino acid residues arranged in a single polypeptide chain with homogeneous amino and carboxyl terminals. Sequence homology with protein AA from other species is quite high with near identity for residues 31 through 54. This sequence is identical to the partial structures for CBA/J mouse AA and serum amyloid A (SAA) previously reported. It is also an exact match to a predicted 73-residue segment from one form of mouse SAA complementary DNA.

Amino Acid Sequence↗
PubMed1986

Localization of human SAA gene(s) to chromosome 11 and detection of DNA polymorphisms.

A human serum amyloid A (SAA) cDNA was used as a probe in chromosome mapping studies to detect human SAA gene sequences in DNA isolated from human/mouse somatic cell hybrids. Southern analysis of DNA from 20 hybrid cell lines, including some with translocations of human chromosomes, placed the SAA gene(s) in the p11----pter region of chromosome 11. Screening of human DNA from unrelated individuals by Southern analysis using the SAA cDNA probe revealed restriction fragment polymorphisms for HindIII and PstI. An analysis of the segregation of these polymorphisms with other markers on the short arm of chromosome 11 should more precisely map the SAA gene(s).

Amyloid↗
PubMed1986

Serum amyloid A in carcinoma of the lung.

Serum concentrations of serum amyloid A protein (SAA), peripheral blood lymphocytes (PBL) mitogenic response to phytohemagglutinin (PHA) and Concanavalin A (Con A), numbers of circulating T- and B-lymphocytes and length of survival after diagnosis were measured in 50 patients with cancer of the lung. SAA levels were significantly elevated when compared to 50 control subjects (P less than 0.001), but did not correlate with state of tumor spread at the time of diagnosis. Mitogenic responses of PBL from the cancer patients to PHA and Con A were significantly depressed (P less than 0.001), but also did not predict state of metastatic spread. The percentage of circulating T-lymphocytes was also significantly depressed in cancer patients when compared to controls. In six patients who survived tumor-free for greater than 2.5 years, SAA serum concentrations returned to normal. Statistical analysis showed a significant correlation between SAA serum concentrations and PBL mitogenic response to Con A. In addition, both high SAA concentrations and depressed PBL responses to Con A correlated with shortened survival. Therefore, these parameters may be of value in evaluating prognosis in patients with lung cancer. In addition, serial monitoring of SAA concentrations may be of value in evaluating recurrence or cure of lung cancer.

Adenocarcinoma↗
PubMed1986

Sex education in the inner city. Learning and retention.

The Discovery program, initiated in 1982, includes two separate one-hour presentations on sex education. It is presented by medical student volunteers to children in the seventh and eighth grades of inner-city public schools. A study including 1,133 youngsters demonstrated a 32% improvement in scores with excellent retention. A control group of 126 students tested three times who did not hear the program demonstrated no learning from the test alone. Socioeconomic status, grade, and sex all influenced the level of knowledge prior to instruction but did not affect the degree of learning. Searches of the medical and educational literature reveal that this appears to be the most thoroughly investigated sex education course in the United States for any grade level. In view of its low cost and ease of implementation, the program could well serve as a model for junior high school sex education curricula in other school systems.

Adolescent↗
PubMed1986

Molecular detection of carriers of hereditary amyloidosis in a Swedish-American family.

Autosomal dominant amyloidosis, also known as familial amyloidotic polyneuropathy (FAP), is a late-onset disorder associated with variants of the protein prealbumin. In FAP Type I, the variant contains a single amino acid substitution at position 30 in the subunit. This substitution corresponds to a single base change in the gene, coincidentally creating a new site for the restriction enzyme NsiI. This change is detectable in the DNA of gene carriers with restriction fragment length polymorphism (RFLP) methods. A well-characterized American family of Swedish origin was studied by this method using a prealbumin cDNA. The RFLP data were found to correlate with previous biochemical characterization of the prealbumin in this family, indicating that this test represents a reliable way to directly detect the DNA mutation responsible for the condition. This test can be used for preclinical diagnosis of gene carriers, including prenatal diagnosis.

Amyloidosis↗