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Biomedical subjects

M D Benson

Publications and source records attributed to M D Benson.

At least 73 records · Page 4Linked to original sources
PubMed1996

Amniotic fluid embolism, anaphylaxis, and tryptase.

It has been recently suggested that amniotic fluid embolism is an anaphylactic reaction to fetal antigens. This hypothesis can be readily tested by obtaining serum tryptase levels within a few hours of the appearance of symptoms in affected patients.

Anaphylaxis↗
PubMed1996

The molecular basis of renal amyloidosis in Irish-American and Polish-Canadian kindreds.

Hereditary amyloidosis of an unusual form has been reported in two separate kindreds; one was Polish-Canadian and the other was Irish-American (Am J Med 1975; 59:121 and Trans Assoc Am Physicians 1981; 94:211). In both kindreds, affected members developed hypertension and nephrotic syndrome due to amyloidosis in their forties or fifties, but the genetic background responsible for the condition has been left undetermined. To identify the genetic defect in these kindreds, a portion of exon 5 of the fibrinogen alpha-chain gene in members of these kindreds was examined for a mutation by single-strand conformation polymorphism analysis and direct DNA sequencing. DNA analyses revealed an A-->T transversion at the second base of codon 526 of the fibrinogen alpha-chain gene in both of these kindreds. Analysis of DNA polymorphisms in the fibrinogen alpha-chain gene locus (TCTT repeat in intron 3, Rsal site in exon 5, and Taql site in the 3' flanking region of the gene) showed the haplotype B5-Rsal(+)-Taql(-) for the Val 526 mutant gene in both kindreds studied here, as well as in two kindreds previously described (J Clin Invest 1994; 93:731). The fibrinogen alpha-chain gene mutation (Val 526) is the genetic defect responsible for hereditary renal amyloidosis in these two kindreds, and the mutant genes in the Val 526 kindreds may have been derived from a single founder.

Adult↗
PubMed1996

Familial and sporadic Alzheimer's disease: neuropathology cannot exclude a final common pathway.

Whether all etiologic forms of Alzheimer's disease (AD) share a final common pathway is a major issue. We determined the severity and regional distribution of neuronal loss, amyloid plaques, neuritic plaques (NPs), and neurofibrillary tangles (NFTs), and calculated the ratio of neuronal loss to NPs and NFTs in brains of 19 familial AD (FAD) patients with linkage to chromosome 14, six AD patients with mutations of chromosome 21 (codon 717 of the beta-amyloid percursor protein gene), and 11 sporadic AD (SAD) patients. There was no difference in the pattern of distribution of the various pathologic features or in the ratio of neuronal loss to NPs or NFTs in any AD group. However, FAD groups could be distinguished from SAD by the greater severity and the lack of influence of apolipoprotein E genotype on pathology. These differences may reflect differences in age at onset rather than different etiopathologic mechanisms. The similarity of pathologic findings in the different AD groups provides evidence for a final common pathophysiologic pathway in AD.

Age of Onset↗
PubMed1996

Amyloidosis of the shoulder in patients on chronic hemodialysis: sonographic findings.

OBJECTIVE: The purpose of this study was to determine the sonographic findings of amyloidosis in shoulders of patients on chronic hemodialysis. SUBJECTS AND METHODS: Sonograms were obtained for 19 shoulders of 11 patients on chronic hemodialysis with clinical findings suggestive of amyloidosis. Five patients had biopsy-proven amyloidosis, and one patient had positive shoulder joint fluid aspirate. The thicknesses of the following structures were measured: the rotator cuff, the subacromial-subdeltoid bursa, and the long head of the biceps tendon and its synovial sheath. The presence of intra- or periarticular masses or nodules, hyperechoic areas, bony erosions, and calcifications was specifically assessed. Shoulder sonograms from dialysis patients were compared with normal sonograms obtained for 20 asymptomatic shoulders of patients without renal disease. RESULTS: The mean rotator cuff thickness in the patients with amyloidosis was significantly greater than that in the normal group (p < .0001). Ten shoulders of six patients with amyloidosis but none of the control subjects had a rotator cuff thickness greater than 7 mm. The synovial sheath of the long head of the biceps tendon was thickened in 10 shoulders of patients with amyloidosis and in one normal shoulder. The subacromial-subdeltoid bursa was thickened in seven shoulders of patients with amyloidosis but not in any shoulders in the control group. Eight shoulder sonograms from dialysis patients showed intra- or periarticular nodules. CONCLUSION: Sonographic findings associated with amyloidosis of the shoulder include thickening of the rotator cuff, the synovial sheath of the long head of the biceps tendon, and the subacromial-subdeltoid bursa and the presence of nodules within or around the joint. Shoulder sonography may be useful as a noninvasive technique for the diagnosis of dialysis-related amyloidosis in the proper clinical setting.

Adult↗
PubMed1995

Tertiary structure of an amyloid immunoglobulin light chain protein: a proposed model for amyloid fibril formation.

An immunoglobulin light chain protein was isolated from the urine of an individual (BRE) with systemic amyloidosis. Complete amino acid sequence of the variable region of the light chain (VL) protein established it as a kappa I, which when compared with other kappa I amyloid associated proteins had unique residues, including Ile-34, Leu-40, and Tyr-71. To study the tertiary structure, BRE VL was expressed in Escherichia coli by using a PCR product amplified from the patient BRE's bone marrow DNA. The PCR product was ligated into pCZ11, a thermal-inducible replication vector. Recombinant BRE VL was isolated, purified to homogeneity, and crystallized by using ammonium sulfate as the precipitant. Two crystal forms were obtained. In crystal form I the BRE VL kappa domain crystallizes as a dimer with unit cell constants isomorphous to previously published kappa protein structures. Comparison with a nonamyloid VL kappa domain from patient REI, identified significant differences in position of residues in the hypervariable segments plus variations in framework region (FR) segments 40-46 (FR2) and 66-67 (FR3). In addition, positional differences can be seen along the two types of local diads, corresponding to the monomer-monomer and dimer-dimer interfaces. From the packing diagram, a model for the amyloid light chain (AL) fibril is proposed based on a pseudohexagonal spiral structure with a rise of approximately the width of two dimers per 360 degree turn. This spiral structure could be consistent with the dimensions of amyloid fibrils as determined by electron microscopy.

Amino Acid Sequence↗
PubMed1995

Characterization of amyloid A protein in human secondary amyloidosis: the predominant deposition of serum amyloid A1.

Serum amyloid A protein (SAA) is the plasma precursor for amyloid A protein (AA), the subunit protein in amyloid deposits of secondary or reactive amyloidosis. Several forms of acute phase SAA have been identified in human plasma. To elucidate whether one of these forms of SAA predominates in the formation of AA amyloid deposits, the amino acid sequence of the subunit protein in six cases of reactive amyloidosis was investigated. Minimal heterogeneity was present at the N-terminus as all samples started with residue 1, 2, or 3 of SAA. The C-terminus, however, was more heterogeneous with the AA protein in each case terminating at multiple sites from residue 58 to 84 of SAA. Since less than 20% of the AA protein in each case contained sequence past residue 67 of SAA, the sequence and recovery of tryptic peptides containing residues 52, 57, and 60 where human SAA1 and 2 differ was used to determine the relative amounts of SAA1 and 2 present. One sample contained only SAA1 sequence, four contained approx. 11% or less of SAA2 sequence, and the sixth contained 24-33% of SAA2 sequence. Thus, while five of the six AA samples contained both SAA1 and 2, the predominant form in all cases was SAA1. In three of the six cases, the protein defensin was isolated along with the AA protein from the fibrils. This may suggest neutrophil involvement in SAA processing to AA fibrils.

Amino Acid Sequence↗
PubMed1995

Haplotype analysis of common transthyretin mutations.

The most frequent transthyretin (TTR) variant associated with hereditary amyloidosis is TTR Met 30, which has its major focus in Portugal, although it also occurs in many other countries. The distribution of the mutation and its occurrence in a CpG dinucleotide lead us to question the origin of the mutation and the possibility of its having originated in Portugal. In order to investigate these questions, we studied the distribution of haplotypes associated with the Met 30 mutation in families from different European countries. All the analysed Portuguese families presented the same haplotype associated with the Met 30 mutation (haplotype I). The same was found for the Swedish and Spanish families studied. However, a distinct haplotype (haplotype III) was found in three families, one Italian, one English and one Turkish. These results suggest that, although the Portuguese Met 30 carriers might have one founder, the mutation probably recurred in populations in Europe in a similar manner to that reported in Japan. In this study, we have also analysed the haplotypes associated with other TTR variants frequent in the Portuguese population.

Amyloidosis↗
PubMed1995

Asp187Asn mutation of gelsolin in an American kindred with familial amyloidosis, Finnish type (FAP IV).

Familial amyloidosis, Finnish type (FAP-IV) was identified clinically in an American kindred with Scandinavian ancestry. A polymerase chain reaction (PCR)-based DNA diagnostic assay was used to identify a G-to-A mutation at position 654 of the gelsolin cDNA (G654A) in this family. Molecular diagnostic testing demonstrated the mutation in individuals in three generations--the clinically affected proband, here deceased clinically affected father, and her presumably affected presymptomatic child. This report represents a rare example of FAP IV and the G654A mutation identified in a family outside Finland. The disease-associated haplotype was similar to that observed in Finnish FAP IV families (suggesting common distant ancestry).

Adult↗
PubMed1995

Sexual behavior in junior high school students.

OBJECTIVE: To evaluate the association between 14 demographic variables and the loss of virginity in a specific sample of junior high school students in Chicago. METHODS: Nine hundred seventy-six students in nine Chicago junior high schools, sixth through eighth grades, were given an anonymous behavior survey (the noncognitive assessment survey). Two separate logistic regression equations were used to determine the relative relationships of the demographic variables to self-reported virginity loss. RESULTS: Five variables were significantly associated with virginity loss in both regression equations. In rank order, they were gender, ethnic group, pubertal status, suicidal ideation, and sibling number (adjusted odds ratio 13.3, 4.57, 3.38, 1.93, and 1.24, respectively). Nine variables did not have a consistent relation with early sexual activity: church attendance, religious affiliation, grade average, housing status, marital status of natural parents, self-esteem, sex education knowledge, school attendance, and chronologic age. CONCLUSIONS: These results call into question two widely held assumptions that form the foundation of many teen pregnancy prevention efforts. First, although many believe that sex education courses can affect behavior, we found no link, either positive or negative, between knowledge of reproductive biology and age of first intercourse. Second, self-esteem level was not associated with age of first intercourse. The variables that did seem related to early sexual activity do not lend themselves to easy manipulation. Our findings suggest that current school-based efforts to alter teen pregnancy rates and sexual behavior are unlikely to succeed.

Adolescent↗
PubMed1995

Cathepsin B generates the most common form of amyloid A (76 residues) as a degradation product from serum amyloid A.

Amyloid A protein (AA), the chief constituent of reactive amyloid deposits, is derived from serum amyloid A (SAA) and most commonly corresponds to the amino-terminal 76 residues (AA76). Digestion of recombinant human SAA1 with a lysosomal thiol protease, cathepsin B, and analysis of the products by SDS-PAGE and amino-terminal sequencing revealed that AA76 was generated as a minor and transient degradation product. Digestion with neutrophil elastase generated intermediates different from AA76. This finding suggests that cathepsin B may play an important role in amyloid fibrilogenesis by converting SAA to AA.

Amino Acid Sequence↗
PubMed1995

In vitro degradation of serum amyloid A by cathepsin D and other acid proteases: possible protection against amyloid fibril formation.

The effects of acid proteases on degradation of serum amyloid A protein (SAA) were investigated in vitro. Human recombinant SAA1 (rSAA1), when incubated with human spleen extracts at pH 3.2, was degraded in the amino-terminal portion of the molecule. This reaction was inhibited by an acid protease inhibitor, pepstatin. The degraded SAA molecules lacking nine or more amino-terminal residues, when exposed to in vitro fibril-forming conditions, failed to form Congo red positive precipitates and did not show amyloid fibril-like structure by electron microscopy. This suggests that the amino-terminal portion of SAA is essential for fibril formation. Cathepsin D, one of the lysosomal enzymes, also initiated degradation of rSAA1 at the amino-terminus. Cathepsin D immunoreactivity was detected in marginal areas of amyloid deposits in spleens from patients with reactive amyloidosis. These findings suggest that cathepsin D or similar acid proteases may be involved in SAA catabolism and may protect against amyloid formation.

Amyloid↗
PubMed1995

A new transthyretin variant (Ser 24) associated with familial amyloid polyneuropathy.

An American kindred with systemic amyloidosis presenting with carpal tunnel syndrome, peripheral neuropathy, and cardiomyopathy is reported. The transthyretin gene of a patient was analysed by direct DNA sequencing and both cytosine and thymine were present at the first base of codon 24. This new point mutation in exon 2 results in the amino acid substitution of serine for proline in the A-B loop of the transthyretin molecule. DNA testing for this mutant allele by restriction fragment length polymorphism analysis based on the polymerase chain reaction is described.

Aged↗
PubMed1995

Low plasma concentrations of retinol-binding protein in individuals with mutations affecting position 84 of the transthyretin molecule.

Retinol-binding protein (RBP), the principal carrier for vitamin A, is known to form a complex with transthyretin (TTR) for transport in plasma. Individuals from a kindred with the amino acid substitution of serine for isoleucine at position 84 (Ser84) of the TTR molecule show substantial reduction in plasma concentrations of RBP. In the present study, we measured plasma RBP in individuals from several kindreds, demonstrating 17 different point mutations within the TTR gene. In each case, these mutations caused single amino acid substitutions at various positions throughout the TTR molecule. Of all the individuals examined, only those with mutations causing amino acid substitutions at position 84 of the TTR molecule (Ser84 and Asn84) demonstrated substantial decreases in plasma concentrations of RBP. These results suggest that the isoleucine at position 84 on the TTR molecule may be critically involved in mediating RBP binding. Further, these findings demonstrate the importance of considering TTR gene mutations when clinically evaluating patients with low RBP.

Humans↗