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Biomedical subjects

J Buxbaum

Publications and source records attributed to J Buxbaum.

At least 37 records · Page 2Linked to original sources
PubMed1989

The spectrum of monoclonal immunoglobulin deposition disease associated with immunocytic dyscrasias.

Immunocytic dyscrasias may be manifested by MIDD often presenting with renal manifestations. The diagnosis is established when deposits are shown by immunopathologic methods to contain a single light-chain isotype in patients who have a monoclonal Ig in the serum or urine, altered kappa:lambda ratio in bone marrow, and/or abnormal biosynthesis of Igs in bone marrow cell cultures. The morphologic expressions of deposits are varied: fibrillar in AL, granular and punctate in LCDD, granular or crystalline in LHCDD, and crystalline in type I cryoglobulinemia.

Amyloidosis↗
PubMed1988

A double monoclonal IgG1 kappa and IgG2 kappa in a single myeloma patient. Variation in clonal products and therapeutic responses.

Two electrophoretically homogeneous immunoglobulins were detected in the serum of a patient with multiple myeloma. The heavy chains were of different classes (gamma 1 and gamma 2). The light chains of both were kappa, but had different electrophoretic mobilities on polyacrylamide gels. Amino acid sequence analysis, carbohydrate determinations, and biosynthetic experiments indicated that the difference seen in their electrophoretic mobility was due to the glycosylation of one but not the other kappa-chain. The primary structure of both chains demonstrated that they both used a V kappa 1 and a J kappa 2 gene segment and the same C kappa allele, Km(1,2), and that both contained the same junctional three amino acid deletion. However, they varied by 19 amino acids in the first 94 amino terminal residues encoded for by the V kappa gene, with some of the substitutions requiring two base changes in the appropriate codons. Moreover, the malignant "clones" producing the two proteins differed in their responses to chemotherapy. These data indicate that, although the two clones producing the serum proteins were different at the time of study, they may have arisen from the same precursor clone.

Amino Acid Sequence↗
PubMed1988

Gamma heavy chain disease in man. Genomic sequence reveals two noncontiguous deletions in a single gene.

A genomic clone was isolated from a human lymphoid cell line which synthesized an NH2-terminally deleted gamma 3 heavy chain disease protein. Nucleotide sequence analysis revealed a normal sequence from 310 bp 5' to the initiator ATG through the codon for VH amino acid 14. Amino acid 15 was derived from the codon for the last J4 amino acid. Thus, the clone contained a deletion of the codons for the VH region beyond amino acid 14, as well as those for the entire D region and most of the J coding region. Some sequence abnormalities were observed in the 400 bp after the deletion. Beyond this, there was excellent homology to published J and intervening sequences, including those containing the enhancer elements. The 1,200-bp switch region was abruptly interrupted by a sequence corresponding to the 3' one-third of CH1. Thus, a second deletion eliminated the acceptor splice site at the 5' end of CH1. When splicing of the primary RNA transcript occurred, the truncated VH region was joined via the J4 donor splice site to the next available acceptor site 5' to the first hinge exon. Hence, the aberrant serum protein was the product of two deletions and a splice correction as well as postsynthetic NH2-terminal proteolysis.

Amino Acid Sequence↗
PubMed1988

Nonamyloidotic monoclonal immunoglobulin deposits lack amyloid P component.

Deposits in tissues from 13 patients with amyloid, 8 with monoclonal light chain or light and heavy chain deposition disease, and 2 with both amyloid and nonamyloidotic light chain deposits of the same isotype were examined in parallel for the presence of amyloid P component by immunofluorescence and/or immunoperoxidase methods. Amyloid P component was detected in the amyloid but not the nonamyloid deposits, even in the 2 individuals in whom both types of deposits were present, indicating a specific relationship between the amyloid P component and the amyloid fibrils.

Amyloidosis↗
PubMed1986

Amyloidosis in subcutaneous heroin abusers ("skin poppers' amyloidosis").

Systemic amyloidosis has recently emerged as a major cause of nephropathy among heroin abusers in New York City. Although focal glomerulosclerosis is typically seen in intravenous drug abusers who present with the nephrotic syndrome, those who escape this complication are at risk for the later development of amyloidosis related to their use of the subcutaneous route. Twenty such addicts identified between 1981 and 1984 are described. Patients typically present with chronic suppurative skin infections, edema, the nephrotic syndrome, benign urinary sediment, and normal-sized or enlarged kidneys. Tubular dysfunction, particularly renal tubular acidosis and diabetes insipidus, is frequent. Progression of renal insufficiency is characteristically rapid. Prolonged survival of heroin abusers and exhaustion of intravenous access requiring recourse to the subcutaneous route underlie the occurrence of amyloidosis in the addict population. Chronic suppurative skin infection consequent to repeated subcutaneous injection appears to be the underlying cause.

Adult↗
PubMed1986

Lack of class I H-2 antigens in cells transformed by radiation leukemia virus is associated with methylation and rearrangement of H-2 DNA.

Transformation of murine thymocytes by radiation leukemia virus is associated with reduced expression of the class I antigens encoded in the major histocompatibility complex (MHC) and increased methylation and altered restriction enzyme patterns of MHC DNA. These changes may play a role in host susceptibility to virus-induced leukemogenesis and accord with the notion that viral genomes play a regulatory function when they integrate adjacent to histocompatibility genes.

Animals↗
PubMed1986

Aberrant immunoglobulin synthesis in light chain amyloidosis. Free light chain and light chain fragment production by human bone marrow cells in short-term tissue culture.

Bone marrow cells obtained from 14 patients with light chain amyloid (AL) deposition were examined by biosynthetic labeling techniques. These analyses identified free monoclonal light chain (L-chain) synthesis even in those patients whose serum or urine contained no M protein or free L-chains or only an intact M protein. The experiments also identified a subset of patients whose plasma cells synthesized polypeptides bearing constant region antigenic determinants that migrated more rapidly than intact L-chains on polyacrylamide gels. Since most AL fibrils contain L-chain fragments rather than intact L-chains, these studies suggested that the genesis of the fibril components may reflect aberrant synthesis, proteolytic processing, or both. We also noted that in some individuals the pattern of Ig synthesis normalized after several courses of cytotoxic therapy. Thus, we could use bone marrow Ig synthesis as a sensitive biochemical parameter for monitoring therapy. Finally, the presence of aberrant synthetic products in these clones raised questions about their origin with respect to the normal processes of transcription, translation, and posttranslational modification in Ig-producing cells.

Amyloidosis↗
PubMed1986

Characterization of renal amyloid derived from the variable region of the lambda light chain subgroup II.

Amyloid fibrils were extracted from the kidney of a patient (CHE) shown to have tetramers and dimers of a monoclonal lambda light chain in his serum, and whose bone marrow cells in short-term culture synthesized these forms and a smaller lambda fragment of approximately 10,000 to 12,000 daltons. Biochemical and serologic analysis of a fraction of a size (obtained from amyloid fibrils extracted from the kidney) similar to that synthesized by the bone marrow cells revealed a light chain fragment corresponding to the amino terminal end of the variable region of the lambda light chain subgroup II. The presence of similarly sized short fragments of lambda light chain in both the synthesized and deposited protein suggests that aberrant synthesis and/or proteolytic degradation may play a pathogenetic role in the process of amyloidogenesis.

Amino Acids↗
PubMed1983

Association of endogenous viral loci with genes encoding murine histocompatibility and lymphocyte differentiation antigens.

Several polymorphic DNA restriction endonuclease fragments hybridizing with xenotropic and ecotropic envelope virus probes map adjacent to minor histocompatibility and lymphocyte (H/Ly) antigen-encoding loci. Viral DNA restriction fragments are associated with Ly-17 on chromosome 1, H-30, H-3, and H-13 on chromosome 2, Ly-21 on chromosome 7, H-28 on chromosome 3, and H-38 (chromosomal location as yet undetermined). In each case no recombinant can be found between the H/Ly locus in question and the virus-related restriction fragment, suggesting that linkage is very tight. Although some viral loci map to locations where no H/Ly has yet been mapped, the frequency and tightness of linkage in the seven instances described, coupled with the large number of as yet unmapped H/Ly loci, suggests that the associations found are significant.

Animals↗
PubMed1982

A study of occlusal relationships and the incidence of myofacial pain.

A survey of 123 subjects (dental students) was performed to evaluate quantitative data that may be of value in the incidence and treatment of myofacial pain. Social statistics, subjective and objective symptoms, and the influence of occlusal interferences on these symptoms were quantitated and recorded. The data indicated that, 123 subjects, 26% had maximum intercuspation of the teeth at terminal hinge closure, 42% had maximum intercuspation of the teeth with the condyles located symmetrically anterior to terminal hinge, and 32.5% had maximum intercuspation of the teeth with assymmetric variations of the condyles anterior to terminal hinge. Averages were obtained for the maximum intercuspal open, the condylar inclination, and the distance anterior from the terminal hinge of both condyles in symmetrical and asymmetrical variations. The location of the transverse (terminal hinge) axis from the external auditory meatus was measured on the ala-tragus line. These latter averages indicate that a significant occlusal discrepancy can result from prevailing techniques of locating an arbitrary hinge axis 10 to 13 mm anterior from the external auditory meatus. The results showed that most subjects demonstrated, both subjectively and clinically, symptoms of neuromuscular dysfunction without occlusal interferences. Therefore, it may be concluded that treatment modalities considered within the first 6 weeks should be conservative and reversible to eliminate or decrease myofascial trigger zones and their areas of referred pain. Alteration of the existing occlusion and maxillomandibular relations may be adjusted with caution, if necessary.

Adult↗
PubMed1981

Nucleotide sequence of a human immunoglobulin C gamma 4 gene.

We report the nucleotide sequence of a gene encoding the constant region of a human immunoglobulin gamma 4 heavy chain (C gamma 4). These data represent the first complete sequence determination of a human CH gene. As expected from structural studies of mouse C gamma genes, the coding sequences for the CH domains and hinge segment are separated from one another by intervening DNA sequences. Comparison with genomic sequences of the mouse C gamma 1, C gamma 2a, and C gamma 2b genes shows conservation of the sequences in the constant region domains and the 3' untranslated region surrounding the presumed site of poly(A) addition.

Amino Acid Sequence↗
PubMed1978

Gamma heavy chain disease in man: translation and partial purification of mRNA coding for the deleted protein.

Lymphoid cells obtained from the peripheral blood of a patient with heavy chain disease have been established in long-term culture. They continue to produce a protein antigenically identical to the deleted gamma3 heavy chain disease protein found in the patient's serum. The availability of the cell line has made it possible to analyze the mRNA coding for this protein. The primary in vitro translation product is 1500-2000 daltons larger than the polypeptide portion of the cytoplasmic or secreted protein and has methionine at the amino terminus. The mRNA sediments at 15.5 S on sucrose gradients and therefore appears to be smaller than the 17S message coding for normal-sized mouse gamma chains. It contains a base sequence that codes for a hydrophobic amino-terminal peptide not found in the cytoplasmic protein. There was no evidence for the synthesis of translatable light chain message by these cells. The present data suggest that this protein results from a primary somatic genetic event that gave rise to a cell product bearing a normal aminoterminus sensitive to limited proteolytic digestion. The serum protein thus appears to begin in the hinge region but, in fact, contains a normal heavy chain initiation site.

Cells, Cultured↗
PubMed1974

IgM-producing tumors in the BALB-c mouse: a model for B-cell maturation.

Five adjuvant induced BALB/c tumors producing IgM-McPc 1748, W 3469, TEPC 183, McPc 774, and Y 5781-were characterized morphologically by electron microscopy, analysis of the distribution of surface-bound and intracytoplasmic IgM using immunofluorescence, and by biochemical study of IgM synthesis, turnover, and secretion. The cells of different tumors appear to represent different stages in B-cell maturation when compared to normal, lipopolysaccharide-stimulated B cells. Thus, McPc 1748 tumor cells resemble 10-25-h stimulated normal B cells, 3469 cells resemble 20-35-h stimulated B cells, TEPC 183 cells resemble 45-65-h stimulated B cells, Y 5781 cells resemble 80-110-h stimulated B cells, and McPc 774 cells resemble 100-130-h stimulated B cells.

Animals↗