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Biomedical subjects

E C Franklin

Publications and source records attributed to E C Franklin.

At least 19 recordsLinked to original sources
PubMed1979

Correlation between fragmented immunoglobulin genes and heavy chain deletion mutants.

It is generally accepted that the variable (V) and constant (C) regions of immunoglobulin (Ig) chains are under separate genetic control. The notion that the different domains and interdomain regions are also under the control of independent genetic units was initially based on the clearcut results obtained by studying the primary structure of deletion mutants and received definitive support from direct analysis of cloned heavy (H) and light (L) chain genes. Here we present additional studies carried out on two selected gamma 3 deletion mutants which indicate the genetic control of human H chains may be even more complex than previously believed.

Base Sequence↗
PubMed1979

Human heavy chain disease protein WIS: implications for the organization of immunoglobulin genes.

Protein WIS is a human gamma3 heavy (H) chain disease immunoglobulin variant whose amino acid sequence is most readily interpreted by postulating that three residues of the amino terminus are followed by a deletion of most of the variable (VH) domain, which ends at the variable-constant (VC) joining region. Then there is a stretch of eight residues, three of which are unusual, while the other five have striking homology to the VC junction sequence. This is followed by a second deletion, which ends at the beginning of the quadruplicated hinge region. These findings are consistent with mutations resulting in deletions of most of the gene coding for the V region and CH1 domain followed by splicing at the VC joining region and at the hinge. These structural features fit well the notion of genetic discontinuity between V and C genes and also suggest similar mechanisms of excision and splicing in the interdomain regions of the C gene of the heavy chain.

Amino Acid Sequence↗
PubMed1979

Subtilisin and cyanogen bromide cleavage products of fibronectin that retain gelatin-binding activity.

The gelatin-binding region of fibronectin has been obtained by subtilisin digestion and cyanogen bromide cleavage of the molecule. Enzymatic digestion yielded two fragments of molecular weights 50,000 (S50K) and 30,000 (S30K) which were isolated by elution from gelatin-Sepharose affinity columns. Because the S50K fragment also mediated the adhesion of fibroblasts to collagen, it contains both the collagen and cell binding sites on the fibronectin molecule. Both fragments had valine as the NH2-terminal residue, were enriched in half-cystine and methionine residues compared to the whole molecule, and were identical by immunodiffusion. The S50K fragment begins with the sequence Val-Tyr-Gln-Pro-Gln-Pro-His-Pro-Gln-Pro-(Pro)-(Gly)-Tyr-Gly-His-( )-Val, a region with an extended conformation which is susceptible to proteolysis and connects this domain to the remainder of the fibronectin molecule. The S50K fragment appears to be located in the COOH-terminal one-third of the fibronectin molecule but does not contain the interchain disulfide bridge(s); the S30K fragment is probably derived from the NH2-terminal region of S50K.

Amino Acids↗
PubMed1979

A new case of gamma heavy chain disease: clinical, immunochemical and structural characterization.

A new case of gamma heavy chain disease (gamma HCD) is described in a 77-year-old woman. The serum and urine contain an M-component and electrophoretic, antigenic and ultracentrifugal properties resembling those of the Fc fragment of IgG globulin. Analysis on SDS-polyacrylamide gel electrophoresis and ultracentrifugal studies show that gamma HCD portein is present in the serum as a dimer with a molecular weight of 58,000 daltons. Analysis of isotypic and allotypic markers along with the structural studies show that this HCD protein belongs to the IgG subclass and that deletion includes the total VH and CH1 regions with sequence starting at residue 225 in the middle of the hinge region.

Aged↗
PubMed1979

Some effects of the administration of endotoxin in mice. Specific cleavage of serum albumin by an acid protease and the generation of amyloid serum component.

Endotoxin has been shown to induce amyloidosis in mice and to result in the appearance in serum of large amounts of amyloidrelated protein (SAA). After injection of 300 mug lipopolysaccharide Escherichia coli, SAA behaves as an acute phase reactant with levels reaching a peak of >600 mug/ml at 18-22 h and returning to base line (<50 mug/ml) by 48 h in each of four strains tested; only the endotoxin-resistant C3H/HeJ strain showed a smaller response. Lesser, though significant, elevations were also found after subcutaneous injection of 25 mg of casein, bovine serum albumin, ovalbumin, or monomeric immunoglobulin G, whereas pyrogen-free human serum albumin/U. S. Pharmacopeia failed to raise SAA levels. SAA generation may thus be a result of endotoxin contamination of these protein preparations. Also present in equivalent amounts in acidified serum from endotoxin-treated mice, but barely detectable in control sera, was a 3,000-dalton molecule whose amino acid sequence is identical to the amino terminal 24 residues of mouse albumin. The appearance of SAA and the amino terminal albumin fragment after endotoxin were unaffected by pretreatment with cobra venom factor, and equivalent levels were found in C5-deficient mice. Pretreatment with pepstatin in vivo, or before acidification in vitro, prevented the appearance of the albumin fragment but had no effect on the appearance of SAA, whereas leupeptin and antipain did not affect the appearance of either SAA or the albumin fragment. These studies suggest that the generation of SAA after endotoxin administration does not involve complement activation or intravascular proteolytic activity, whereas the liberation of a specific peptic-like cleavage product of albumin appears to be the consequence of an acid protease.

Amino Acid Sequence↗
PubMed1978

Degradation of serum amyloid A protein by surface-associated enzymes of human blood monocytes.

Peripheral blood monocytes incubated in a serum-free medium degraded serum amyloid A (SAA) protein along three pathways. Of 20 normal subjects, 8 degraded SAA completely with no detectable intermediates. Eight subjects transiently produced an amyloid A (AA)-like intermediate which comigrated on sodium dodecyl sulfate-polyacrylamide gel electrophoresis (PAGE) with tissue AA protein and reacted with antisera to AA, whereas four subjects yielded a persistent AA-like intermediate on PAGE. This group also failed to degrade tissue AA protein. Cells from 10 patients with amyloidosis fell into the second group. The responsible enzymes appear to be serine proteases because they are inhibited by disopropyl fluorophosphate. They were not affected by epsilon-amino caproic acid, L-1-tosylamide-2-phenylethyl chloromethyl ketone, or N-alpha-p-tosyl-L-lysine chlormethyl ketone. It appears possible that the enzymes are associated with the outer membrane of the cell because only a small fraction of the activity is secreted into the medium and because enzyme activity remains after fixation of the cells with glutaraldehyde which completely stops phagocytosis. Perhaps differences in patterns of proteolysis may play a role in the predisposition to amyloidosis.

Amyloid↗
PubMed1978

The structural heterogeneity among degraded gamma heavy chain disease proteins.

The amino terminal sequence of seven newly studied and three previously reported gamma Heavy Chain disease proteins show that they begin at several sites ranging from position 215--234 in the hinge region. The presence of more than one species of molecule in several of the sera and the susceptibility of this region to proteolytic cleavage, taken together with the finding of a blocked Heavy Chain disease protein in the serum of one and the cells of another patient support the concept that these molecules are the result of proteolytic cleavage of typical Heavy Chain disease proteins.

Amino Acid Sequence↗
PubMed1978

Arthralgias and arthritis in viral infections.

Arthritis and arthralgias are common in many viral infections. They are particularly prominent with hepatitis B virus and rubella infection, where they may be the major presenting symptom. "Lyme arthritis" is also associated with a virus. Similar symptoms are occasionally seen with adenovirus, Coxsackie and echovirus infection. Joint lesions are due to the deposition of immune complexes and not direct viral infection. While the arthritis is usually transient and self-limited, the physician must consider viral infections as etiologic agents of arthralgias and arthritis.

Adult↗
PubMed1978

An unusual case of a plasma cell neoplasm with an IgG3lambda myeloma and a gamma3 heavy chain disease protein.

A unique case of gamma3 heavy chain disease with two related serum proteins is reported. One molecule appears to be an IgG3lambda myeloma protein. The second molecule is a dimer of a shortened gamma3 heavy chain that has an unblocked amino terminus and lacks the VH and CH1 domains. Its probable origin as a synthetic product is discussed. The clinical and pathologic features of this patient resemble those of other patients with gamma heavy chain disease more than those of patients with multiple myeloma. It seems likely that the heavy chain disease protein is the result of a mutational event in the malignant clone originally producing the myeloma protein.

Centrifugation, Density Gradient↗
PubMed1978

Polymorphism of tissue and serum amyloid A (AA and SAA) proteins in the mouse.

Amino acid sequence studies of the amino terminal 25 residues of amyloid A (AA) protein and the serum precursor (SAA) induced with casein or LPS indicate differences in the sequence at position 6 and significant heterogeneity at several other positions in SAA. These findings suggest that SAA is a polymorphic serum protein and raise the possibility that only certain forms of SAA are processed to the tissue amyloid fibril.

Amino Acid Sequence↗
PubMed1977

Association between hepatitis B virus and essential mixed cryoglobulinemia.

In view of a high frequency of liver involvement in patients with essential mixed cryoglubulinemia, we looked for evidence for hepatitis B virus infection in 25 serum specimens and 19 cryoprecipitates obtained from 30 patients. Three of the 25 serum specimens contained Hbs Ag, and 12 had antibody. The frequency of positive results was increased to six and 11 of 19 respectively when cryoprecipitates were examined, and 14 of 19 (74 per cent) of the cryoprecipitates were positive for either HBs Ag or its antibody. Electron microscopy of four cryoprecipitates showed structures resembling the 20-nm and 27-nm spheres, tubules, as well as the Dane particles characteristic of hepatitis B virus infection. Since such infection appears to be involved in the pathogenesis of the syndrome, the term "essential mixed cryoglobulinemia" should be replaced by "mixed cryoglobulinemia secondary to hepatitis B virus" or perhaps to other viral infections.

Aged↗