Heavy chain disease of the gamma (gamma M) type: report of the first case.
TL;DR: The serum of a patient with chronic lymphocytic leukemia, and amyloidosis, was found to contain an unusual protein with µ chain antigenic determinants that was devoid of light chains and was present in the form of multiple disulfide linked polymers.
About: This article is published in Blood.The article was published on 1970-08-01 and is currently open access. It has received 103 citations till now. The article focuses on the topics: Heavy chain disease & Bence Jones protein.
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TL;DR: The findings suggest that although WDL, CLL and well differentiated lymphoproliferative diseases with monoclonal gammopathy are histologically similar, their clinical and hematological presentations differ sufficiently to justify their separation into three distinct entities.
Abstract: A clinicopathologic analysis of 108 patients originally diagnosed as malignant lymphoma, well differentiated lymphocytic type on the basis of lymph node (l.n.) biopsy sections showed that in 41 patients neither absolute lymphocytosis nor monoclonal gammopathy was evident (Group I). A monoclonal serum immunoglobulin was present in 20 patients, 18 of whom had no absolute lympocytosis (Group II). The remaining 47 patients had absolute lymphocytosis (above 4,000/mm3) and no monoclonal gammopathy (Group III). Of the 41 Group I patients, 11 had no bone marrow involvement at the time of 1.n. biopsy and 35 never developed lymphocytosis over follow-up periods ranging from 24 to 150 months. Our observations indicate that malignant lymphoma of the well differentiated lymphocytic type (WDL) may be a tissue manifestation of chronic lymphocytic leukemia (CLL) but may also exist as a distinct form of non-Hodgkin's lymphoma. Of the 20 patients with monoclonal gammopathy (Group II) 90% had plasmacytoid lymphocytes and/or plasma cells in tissue sections. However, these cells were also present in 9.7% of patients with WDL (Group I) and in 7% of patients with CLL (Group III) without demonstrable monoclonal gammopathy. Our findings suggest that although WDL, CLL and well differentiated lymphoproliferative diseases with monoclonal gammopathy are histologically similar, their clinical and hematological presentations differ sufficiently to justify their separation into three distinct entities. At the same time they could well represent different hematopathologic expressions of the same basic process, namely a proliferation of small lymphocytes usually of the B-cell type.
166 citations
TL;DR: The natural history and clinico-pathological patterns of these diseases may, especially in the case of a chain disease, constitute a model providing unique opportunities for research into the pathogenesis of human lymphoid malignancies.
Abstract: Human heavy chain diseases are lymphoproliferative disorders characterized by the production of immunoglobulin molecules consisting of incomplete heavy chains devoid of light chains. Heavy chain diseases of the three main immunoglobulin classes have been described. Since the description ofthe first case by Franklin et al. (1964), close to 50 patients with gamma heavy chain disease have now been reported. The most frequent condition within the group of heavy chain diseases is a-chain disease (Seligmann et al. 1968) with more than 150 cases presently known to us. In contrast, /^-chain disease appears to be relatively rare since only 15 cases have been reported since its first description (Forte et al. 1970). Heayy chain diseases raise a number of interesting problems related to various fields such as the structure of the abnormal immunoglobulin, and the cellular genetic mechanisms responsible for the synthesis of a deleted heavy chain and, in most instances, the lack of production of light chains. In addition, the natural history and clinico-pathological patterns of these diseases may, especially in the case of a chain disease, constitute a model providing unique opportunities for research into the pathogenesis of human lymphoid malignancies.
148 citations
01 Jan 1978
128 citations
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TL;DR: Sucrose gradient centrifugation is found to be a suitable method for determining sedimentation coefficients of enzymes in protein mixtures and the sedimentation behavior of several of the enzymes in the pathway of histidine biosynthesis in S. typhimurium has been determined.
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TL;DR: An hypothesis is presented to relate the structural features of the various γ-globulins in terms of the multiplicity of polypeptide chains in these molecules.
Abstract: When human and rabbit 7S γ-globulins were reduced in strong urea solutions by a number of procedures, their molecular weights fell to approximately ⅓ of the original values. Partial separation of the reduction products was achieved using chromatography and starch gel electrophoresis in urea solutions. One of the components of reduced human 7S γ-globulin was isolated by chromatography, identified by starch gel electrophoresis, and subjected to amino acid analyses. The amino acid composition of this component differed from that of the starting material and also from that of the remaining components.
A reduced pathological macroglobulin dissociated to components with an average molecular weight of 41,000. Several reduced human myeloma proteins, when subjected to starch gel electrophoresis, yielded individual patterns that nevertheless had features in common with those of reduced normal γ-globulins. Reduction of normal and abnormal γ-globulins was accompanied by the appearance of titratable sulfhydryl groups. Chemical treatments other than reduction were used to determine the type of bond holding the subunits together. It was tentatively concluded that they were linked by disulfide bonds. An hypothesis is presented to relate the structural features of the various γ-globulins in terms of the multiplicity of polypeptide chains in these molecules.
382 citations