Search PubMed⌕ Search

Biomedical subjects

M D Benson

Publications and source records attributed to M D Benson.

At least 181 records · Page 10Linked to original sources
PubMed1985

Isolation and characterization of amyloid protein AA in the Abyssinian cat.

Amyloid fibrils were isolated by extraction in deionized water from the kidneys of an Abyssinian cat with familial renal amyloidosis. The fibrils were suspended in a buffer containing 6 M guanidine hydrochloride and reduced and alkylated using dithiothreitol and iodoacetid acid. The resulting amyloid fibril subunit protein was isolated by chromatography on a column of Sepharose CL6B. It was fragmented using cyanogen bromide, and the resultant peptides were separated by reverse phase high performance liquid chromatography. The protein was characterized by determination of the amino acid sequence of the cyanogen bromide fragments using a Beckman 890C sequencer. The primary structure of this amyloid fibril subunit protein showed strong homology with amyloid protein AA found in man and animals with spontaneous and experimentally induced reactive systemic amyloidosis. This study confirms the reactive nature of familial renal amyloidosis in the Abyssinian cat and suggests that this disease may be a valuable spontaneous animal model for the study of familial Mediterranean fever in man.

Amino Acid Sequence↗
PubMed1984

Primary structure of an amyloid prealbumin and its plasma precursor in a heredofamilial polyneuropathy of Swedish origin.

Prealbumin from an individual with heredofamilial amyloid polyneuropathy of Swedish origin was isolated from plasma by using a three-step procedure involving ion exchange, Affi-gel Blue affinity chromatography, and gel filtration. This prealbumin and its associated amyloid fibril subunit protein were digested with trypsin and the resulting peptides were separated by high performance liquid chromatography. Comparison with normal prealbumin peptides showed that an amino acid substitution of a methionine for a valine had occurred at position 30. In the plasma prealbumin, the abnormal residue accounted for 1/3rd of the material while in the amyloid fibrils it accounted for 2/3rds. From this sequence information and the known three-dimensional structure of the prealbumin molecule, a mechanism for the amyloid formation is proposed. It involves formation of the amyloid fibrils by addition of prealbumin dimers or tetramers to the aggregate. Each dimer must contain at least one variant peptide chain while the tetramer must contain at least two abnormal chains. Either of these models can account for the observed amount of normal prealbumin in amyloid fibrils. No proteolytic processing of this molecule is required because the entire undegraded prealbumin molecule is found in the fibrils.

Amino Acid Sequence↗
PubMed1984

DMSO and colchicine therapy in amyloid disease.

There is no specific therapy for primary amyloidosis, and acquired generalised amyloidosis can be treated only if the underlying disease is eliminated. In this study we have investigated the role of colchicine therapy in primary amyloidosis, and dimethylsulphoxide (DMSO) in leprosy associated secondary amyloidosis. No effect on creatinine clearance or 24 h proteinuria could be observed in the patients with primary amyloidosis. In the DMSO group renal function was considerably improved in 3 patients with moderate renal failure but not in those with severe renal impairment (creatinine clearance less than 10 ml/min). Serum SAA determinations were not particularly informative. These findings point to a beneficial effect of DMSO in human secondary amyloidosis when given at an early stage of renal involvement.

Amyloidosis↗
PubMed1983

Polymorphism of human plasma thyroxine binding prealbumin.

Amyloid fibrils from an individual with heredofamilial amyloidosis were found to be composed of plasma prealbumin. To study this protein a three step procedure to isolate prealbumin from plasma was developed. It entailed ion exchange chromatography on DEAE Sephadex, affinity chromatography on Affi-gel Blue and gel filtration on AcA-34. Trypsin Digests of prealbumin were separated by reverse phase HPLC and the pattern compared to that from the normal protein. Only one unexpected peptide was found and it represented the substitution of a methionine for a valine at position 30 in the molecule. This substitution accounts for about 1/3 of the isolated molecules and it represents the first point mutation identified in human plasma prealbumin.

Amino Acid Sequence↗
PubMed1983

Erosive arthritis in hereditary amyloidosis.

Nine patients from 2 distinct kindreds with familial amyloidosis had episodes of inflammatory arthritis and radiographic evidence of joint erosions. Histologic features from erosive lesions in both kindreds showed proliferation of synovium with erosive bone and cartilage change. No large amyloid deposits were seen. This study indicates that an erosive synovitis of unknown cause may be a feature of some forms of hereditary amyloidosis.

Aged↗
PubMed1983

Prealbumin and retinol binding protein serum concentrations in the Indiana type hereditary amyloidosis.

Serum prealbumin and retinol binding protein (RBP) concentrations were determined for 68 members of a kindred in Indiana with a familial type of systemic amyloidosis. Immunohistochemical studies on rectal and muscle biopsy material from individuals with this type of amyloidosis revealed staining of amyloid deposits with anti-prealbumin. Both the serum prealbumin and RBP concentrations were significantly depressed in 9 patients with amyloidosis when compared with normal controls and unaffected kin. In addition, the mean RBP serum concentration of 21 offspring of the patients with amyloidosis was significantly depressed. A more significant finding was that on the basis of the serum RBP concentrations, the offspring could be divided into 2 distinct groups. One group represented approximately 50% of the children and had serum prealbumin and RBP concentrations not significantly different from their afflicted parents. The second group had serum prealbumin and RBP concentrations not significantly different from those of normal controls and non-affected kin. These findings show that prealbumin and RBP serum concentrations are depressed in patients with the Indiana type of hereditary amyloidosis and that these serum abnormalities may be present long before development of clinical disease. They suggest that individuals with this genetic abnormality may be identified prior to clinical expression of the disease.

Adolescent↗
PubMed1983

Ovarian tumor antigens.

Increasing knowledge of tumor immunology and particularly of tumor-associated antigens (TAAs) has great potential in the diagnosis of and therapy for ovarian cancer. The use of hybridoma-produced monoclonal antibodies is likely to improve the specificity of radioimmunoassay and thereby aid laboratories in the identification of additional TAAs. Over a dozen TAAs are useful in the diagnosis and follow-up of ovarian cancer, and more have been described recently, although none are currently of value for screening. Cure of a mouse ovarian cancer has been reported with the use of antibodies to TAAs. Preliminary studies utilizing injection of heterologous antibodies to TAAs in women with ovarian cancer are already under way. The minimal toxicity encountered thus far suggests that this method may be a viable therapeutic modality in the future.

Antigens, Neoplasm↗
PubMed1982

SAA suppression of immune response in vitro: evidence for an effect on T cell-macrophage interaction.

SAA has been shown previously to inhibit the in vitro antibody response of normal murine spleen cells to SRBC. This effect is nonspecific but does not directly suppress B cells. To evaluate the mechanisms of this suppression, the in vitro antibody response to SRBC was studied using cells from cytoxan-treated mice. No evidence for preformed suppressor cells was found. Also, preincubation of normal cells with SAA failed to reveal evidence for the generation of suppressor cells in vitro. The addition of 2-mercaptoethanol to cultures completely reversed the suppression caused by SAA. Addition of either normal T cells or normal macrophages to cultures partially reversed suppression caused by SAA, but only a combination of T cells and macrophages could completely reverse the suppression. These data are consistent with an effect of SAA on macrophage-T cell interaction in the generation of the immune response to T-dependent antigen. No evidence for the participation of suppressor cells as has been demonstrated for alpha-fetoprotein was found.

Amyloid↗
PubMed1981

Partial amino acid sequence homology between an heredofamilial amyloid protein and human plasma prealbumin.

Amyloid fibril protein has been isolated from the tissues of a patient of Swedish ancestry with autosomal dominant heredofamilial amyloidosis. After solubilization in guanidine HCl, a significant amount of the protein was contained in a homogeneous low molecular weight fraction. Molecular weight of approximately 14,000, amino acid analysis, double immunodiffusion analysis and immunoelectrophoresis all supported this material being a prealbumin-related protein. Automated sequence analysis gave a mixture of amino acids at each step, suggesting an heterogeneous NH2-terminus. After cleavage of the protein with cyanogen bromide, a homogeneous peptide was obtained with the sequence Val-Val-Val-Leu-Asp-Ala-Val-Arg-Gly-Thr-Pro- corresponding in 9 of the 11 positions analyzed with the known sequence of human prealbumin, starting with position 14. Antiserum raised to the amyloid protein reacted with normal human prealbumin. After absorption with normal human serum, this antiserum continued to detect a determinant in the amyloid patient's serum, suggesting an abnormal serum prealbumin, which may be the precursor of the fibril protein in this type of heredo-familial amyloidosis. Indirect immunohistochemical studies on kidney tissue from the patient with amyloidosis showed marked staining with anti-prealbumin and anti-heredofamilial amyloid protein, but not with anti-AA or anti-kappa antisera. No genetic association between this family and amyloidosis and Portuguese families with familial amyloid polyneuropathy is known.

Amino Acid Sequence↗
PubMed1981

Suppression of in vitro antibody response of human peripheral blood lymphocytes by a heat-labile factor in normal human serum.

When fresh autologous serum was added to normal human peripheral blood lymphocytes (PBL), it suppressed greater than 90% of the in vitro anti-SRBC response of these cells. Heating the serum for 30 min at 56 degrees C reversed this suppression, Serum from a patient with rheumatoid arthritis and circulating immune complexes had no suppressive effect on the anti-SRBC response of normal human PBL, but serum from patients having the same disease, without circulating immune complexes, did suppress over 90% of the plaque-forming cell response. Serum from an agammaglobulinaemic patient was also suppressive. Addition of serum from patients with congenital deficiencies of C2, C3, C5 and C8 also has a suppressive effect. Absorption of normal serum with immune complexes markedly decreased levels of C1 and C4, and also reversed the suppressive effect of this serum. These data suggest that a heat-labile factor in normal human serum which can be absorbed by immune complexes suppresses the antibody response to a T-dependent antigen. Other immune suppressors found in normal human serum are heat-stable or do not suppress in the presence of normal serum proteins. Thus the suppressive protein described in these studies may be unique. It is possible that either C1 or C4 or both may play a role in the suppression noted here.

Agammaglobulinemia↗
PubMed1981

Serum amyloid A induction does not require the spleen.

Our results indicate that serum amyloid A induction does not require the spleen, and further, the kinetics of serum amyloid A induction suggest that the phase of marked increase is likely to be related to the acute inflammatory reaction.

Amyloid↗
PubMed1980

Serum amyloid protein levels in south american children with rheumatoid arthritis: a co-operative study.

Serum amyloid protein (SAA) levels were determined by radioimmunoassay in 90 children with juvenile rheumatoid arthritis (JRA). Significantly higher levels of SAA were present in children with the polyarticular and systemic forms of the disease. SAA levels correlate with disease activity, increasing during acute exacerbations, decreasing during remission and in patients having prednisone therapy. High serum SAA concentrations in children with JRA did not correlate with the presence of secondary amyloidosis and may be useful as a disease monitor.

Amyloid↗
PubMed1980

Methylprednisolone pulse therapy for nonrenal lupus erythematosus.

High-dose intravenous methylprednisolone therapy has previously been shown to be efficacious in the treatment of renal lupus erythematosus. The present report presents 2 patients with life-threatening, nonrenal lupus erythematosus. One patient had coma and seizures, while the other had sever thrombocytopenia and anaemia. Both had failed to respond to oral corticosteroid therapy in high doses but had dramatic clinical responses with intravenous methylprednisolone given in 'pulses.' Possible mechanisms of clinical improvement are discussed.

Adult↗