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Biomedical subjects

M D Benson

Publications and source records attributed to M D Benson.

214 records · Page 12Linked to original sources
PubMed1975

Antigenicity and cross-reactivity of denatured fibril proteins of primary, secondary, and myeloma associated amyloids.

Antisera have been produced against amyloid fibril preparations of primary, secondary, and myeloma origins. These have revealed the presence of both idiotypic and shared antigenic determinants. A high degree of cross-reactivity among the 3 types of amyloid has been found irrespective of classification. One antiserum to a secondary amyloid fibril preparation proved to be directed against A protein (the major nonimmunoglobulin constituent of secondary amyloid fibrils). This antiserum detected A protein in several of the secondary amyloids as well as in two primary amyloid fibril preparations which were degraded with alkali; These finding indicate that amyloid fibrils of various origins have similarities in composition and, therefore, may have common factors involved in fibrillogenesis.

Amyloid↗
PubMed1975

Amyloid fibril protein related to immunoglobulin lambda-chains.

Amyloid fibrils, isolated from the spleen of a patient with primary amyloidosis, had an N-terminal sequence showing a high degree of homology with lambda Bence Jones proteins. Anti-serum prepared to the amyloid protein detected a soluble factor, antigenically identical to the isolated fibril preparation.

Amino Acid Sequence↗
PubMed1974

Isolation and identification by sequence analysis of experimentally induced guinea pig amyloid fibrils.

Amyloidosis was produced experimentally in guinea pigs by multiple casein injections. Amyloid fibrils were isolated and fractionated and a protein obtained that had an amino acid composition comparable with A protein, a unique nonimmunoglobulin constituent of secondary amyloid deposits. N-terminal sequence analysis demonstrated a sequence homologous with that of A proteins from human and monkey preparations but preceded by a 5-residue peptide which had an N-terminal histidine. A definite species specificity in A protein from human and guinea pig was identified on immunologic analysis.

Amino Acid Sequence↗
PubMedDate not supplied

P-component of amyloid. Isolation from human serum by affinity chromatography.

Human amyloid P-component was isolated from plasma by affinity chromatography utilizing antiserum to tissue P-component coupled to Sepharose 4B. Characterization and comparison of the isolated P-component proteins from tissue and plasma demonstrated immunologic identity and identical RF values of polyacrylamide disk gel electrophoresis. Amino acid analyses of P-components from two individual plasmas were comparable, but some variations from tissue P-component were noted. Attempts to perform amino acid sequencing on the plasma protein were unsuccessful. Electron microscopic studies revealed that the plasma P-component had a pentagonal ultrastructure identical to the tissue P-component. These studies compared similarities of tissue and plasma P-components and revealed the unique pentagonal ultrastructure of the plasma protein.

Alpha-Globulins↗
PubMedDate not supplied

Identity of a peritoneal fluid immunoglobulin light chain and the amyloid fibril in primary amyloidosis.

A monoclonal immunoglobulin has been isolated from the peritoneal fluid of a patient with primary amyloidosis. The immunoglobulin was reduced and alkylated and the light and heavy chains were compared to the major protein constituent of that patient's hepatic amyloid fibrils. N-terminal amino acid sequences of the light chain and amyloid fibril were identical when carried to 20 residues and were typical of a kappa I light chain. Molecular weight studies suggested that the fibril protein was composed of an intact light chain with a molecular weight of 23,000. The hypothesis that amyloid fibril protein in primary amyloid is derived from circulating monoclonal immunoglobulin is discussed.

Amino Acid Sequence↗
PubMedDate not supplied

"A" protein of amyloidosis. Isolation of a cross-reacting component from serum by affinity chromatography.

A nonimmunoglobulin protein (A protein) has been isolated from amyloidotic tissue of secondary type. Antisera prepared to this protein identified a cross-reacting substance in the sera of patients with secondary amyloidosis. Sera from 70 persons with amyloidosis, 120 normal adults, 20 aged persons, and 97 patients with chronic diseases were tested for this substance. One hundred percent of secondary amyloid sera had amounts of amyloid serum component detectable by double diffusion in agar, whereas only 19 percent of primary amyloid sera were positive. Approximately 60 percent of rheumatoid sera as well as 60 per cent of sera from aged individuals were positive. Only 3 percent or normal blood donors had detectable amounts of this circulating substance. Isolation of the serum component by affinity chromatography and partial characterization have shown that it is an alpha-globulins with a molecular weight of 100,000-120,000, that it is not related antigenically to immunoglobulin or amyloid P-compoment, and that it has an amino acid analysis that is markedly different from tissue A protein. The possible participation of this substance in the genesis of amyloid is discussed.

Adult↗
PubMedDate not supplied

The pathogenesis of reactive systemic amyloidosis.

The diagnosis of amyloidosis is based on the presence of extracellular tissue deposits of proteinaceous material that demonstrate a characteristic green color when stained with Congo red and viewed under polarized light. Several different proteins are amyloidogenic but, in domestic animals, spontaneously occurring systemic amyloidosis is reactive in nature and characterized by the presence of amyloid protein AA. This type of systemic amyloidosis may occur secondary to chronic inflammatory or neoplastic disease, but in many instances no predisposing disease is found. A sustained increase in the serum concentration of serum amyloid A protein (SAA) is necessary but not sufficient for the development of reactive amyloidosis. Other inherited and acquired host-related factors are likely to be important in the development of reactive amyloidosis because this condition develops in few patients with chronic inflammatory disease. The tissue tropism of amyloid deposits varies with the amyloid protein itself and species affected. The consequences of amyloidosis for the host depend upon the tissues involved and the response of these tissues to the presence of the amyloid deposits. In domestic animals, reactive systemic amyloidosis is nephropathic, leading to end-stage renal disease, and the clinical presentation is that of uremia.

Amyloidosis↗
PubMedDate not supplied

Therapeutic equivalents in clinical practice.

With increasing debate over the rising expenses of health care, a variety of cost-saving measures has been attempted over the years. Use of primary care physicians as "gate keepers," reduction in the length of hospital stays, and pushing women toward vaginal birth after Cesarean section have all been utilized despite on going issues with patient satisfaction and even safety. One remarkable success in stretching health-care dollars that has often been overlooked is the prescription of therapeutic equivalents, or generic drugs. Although available on a limited basis for decades, off-brand manufacture of pharmaceuticals with identical active ingredients as those of the branded drug received a large boost through Congressional legislation in 1984 with the Hatch-Waxman Act. "Fast-track" FDA approval was initiated by Congress to introduce competition into the marketplace for drugs whose patients had expired. While giving close scrutiny to the manufacturing process and requiring the same level of regulatory supervision for factors such as bioavailability and shelf life, the Hatch-Waxman Act removed the burden and expense from generic manufacturers of proving the safety and efficacy all over again of a previously FDA-approved drug. With less than a 20% market share of all prescribed drugs in 1984, the generic drug industry has captured roughly 44% of the market in recent years while accounting for only 8% of expenditures on prescription medication. The prescription of therapeutic equivalents is one method of keeping health care costs down without compromising patient satisfaction or safety.

Drug Approval↗
PubMedDate not supplied

The effect of gold salts on casein-induced macrophage activation and serum amyloid protein SAA levels.

Previous work from our laboratory has demonstrated a marked inhibitory activity of Auranofin (Au) and Gold Sodium Aurothiomalate (GST) on monocyte-macrophage function and an important role for macrophages in the pathogenesis of casein-induced experimental amyloidosis. In the present study we have looked at the in vivo effect of Au and GST on the inhibition of casein-induced macrophage activation and serum SAA levels. Au and GST markedly inhibited casein-induced macrophage activation while only Au reduced serum SAA levels to a significant degree. The present data raises the possibility that Au may be helpful in the treatment of secondary amyloid disease.

Animals↗
PubMedDate not supplied

SAA amyloid protein levels in amyloid-prone chronic inflammatory disorders. Lack of association with amyloid disease.

Serum amyloid protein A (SAA) levels were evaluated by a sensitive radioimmunoassay technique in leprosy, juvenile rheumatoid arthritis and chronic osteomyelitis. SAA was elevated in all 3 groups of patients. The level in each of the patient groups did not reflect the presence of secondary amyloidosis. Our study suggests that serum SAA protein levels should not be considered a routine diagnostic test in patients with chronic inflammatory diseases prone to the development of amyloid disease.

Amyloid↗