Heavy Chain Phenotype Research Articles

Repression of the embryonic myosin heavy chain phenotype in regenerating chicken slow muscle is dependent on innervation.

Ventricular-like and fast myosin heavy chains (VL-MHC and FMHC) are transiently expressed during slow skeletal muscle development. The influence of innervation on repression of these MHC isoforms is investigated over an 84-day time course in: (1) normal anterior latissimus dorsi (N-ALD) muscles, (2) regenerating ALD (R-ALD) muscles, (3) denervated ALD (D-ALD) muscles, and (4) regenerating and denervated ALD (RD-ALD) muscles. Western blotting demonstrates that the VL-MHC is expressed in R-, D-, and RD-ALD muscles, but not in N-ALD muscles. Expression of the VL-MHC is transient in R-ALD muscles. In contrast, VL-MHC expression persists in RD-ALD muscles, and appears with time in D-ALD muscles. FMHC was not detected in N-ALD muscles by Western blotting. Two FMHCs are seen in R-ALD and RD-ALD muscles, and in 13-day embryonic ALD muscles. The slower migrating FMHC (FMHCA) comigrates with developmentally regulated FMHCs in fast pectoralis muscle, while the faster migrating FMHC (FMHCB) comigrates with the faster migrating FMHC in embryonic ALD muscle (13 days in ovo). FMHCB decreases in amount over the time course in R-ALD muscles, while FMHCA persists. In contrast, substantial levels of both FMHCs persist in RD-ALD muscles, and appear with time in D-ALD muscles. The cellular distribution of MHCs is followed by immunocytochemistry. Regenerating cells expressing VL-MHC and FMHC are replaced by a mature population in R-ALD muscles. Some of the mature myofibers in R-ALD muscles express FMHC, but not VL-MHC. In RD-ALD and D-ALD muscles, both regenerating and mature muscle cells are seen which express VL-MHC and FMHC. Our results indicate that innervation is required for the repression of VL-MHC and FMHCB during regeneration of slow muscle.

Expression of Various NCAM Isoforms in Human Embryonic Muscles: Correlation with Myosin Heavy Chain Phenotypes

Neural cell adhesion molecules (NCAM) are known to play a pivotal role in regulating cell-cell interactions in various tissues. The diversity of NCAM is made by alternative splicing of a single gene and by post-translational modifications. The spatio-temporal expression of the various isoforms is developmentally regulated and may modulate cell interactions. We investigated the expression of NCAM isoforms, in particular polysialylated and phosphatidylinositol-anchored isoforms, in developing psoas and quadriceps human muscle from 15 weeks of gestation to term. In parallel, we examined the expression of the myosin heavy chain phenotype (another developmentally regulated system) to determine whether polysialylated-NCAM molecules (the so-called embryonic NCAM) and developmental myosin heavy chains are coexpressed. Our results showed an expression of polysialylated-NCAM and phosphatidylinositol-anchored isoforms during the early stages of myotube maturation. The expression of polysialylated-NCAM on developing myotube was always associated with the expression of developmental myosin heavy chains. However, the loss of polysialylated-NCAM from maturing myotubes was not correlated with the disappearance of the developmental myosin heavy chains, but rather with the appearance of an adult myosin heavy chain phenotype. The relationship between polysialylated-NCAM and myosin heavy chain phenotype was similar in psoas and in quadriceps muscles. We observed that maturation of quadriceps muscle takes place earlier than psoas. Biochemical analysis showed that phosphatidylinositol-anchored molecules were never polysialylated; this indicates different roles of these isoforms in muscle development.

Immunoglobulin allotypes are not associated with HLA-antigens, autoantibodies and clinical symptoms in systemic lupus erythematosus

Immunoglobulin heavy chain (G1m, G2m, G3m, A2m) and kappa light chain (Km) allotype and phenotype frequencies of 323 central European Caucasian patients with systemic lupus erythematosus (SLE) were examined and correlated with various genetic, serologic and clinical markers of SLE. No significant associations were found between immunoglobulin allotypes or phenotypes and all 20 parameters tested (nephritis, vasculitis, arthralgias, photosensitivity, discoid lesions, central nervous system disease, Raynaud's phenomenon, sex, anti-Ro, anti-La, anti-nRNP, HLA-DR1-DR7, HLA phenotypes B8-DR3, B7-DR2). It could therefore be assumed that Gm, A2m and Km allotypes were not associated with HLA-antigens and had no influence on the serologic and clinical expression of SLE.

Regulation of myosin heavy chain and actin isogenes expression during cardiac growth

The cardiac ventricular myosin heavy chain phenotype is developmentally and hormonally regulated, but less is known concerning the actin phenotype. In this study, the levels of accumulation of alpha-skeletal and alpha-cardiac actin mRNAs were investigated in rat and human ventricles by primer extension assays. In rat, the two iso-mRNAs are present in approximately equal amounts from birth until 15 days of age and the cardiac form is predominant in adult and senescent hearts. Hypothyroid development has no effect, at least during the first two weeks of age. In man, the two isoactins are co-expressed to similar ratios in one control heart and in one failing heart. It therefore appears that myosin heavy chain and actin multigene families are both expressed in a species specific fashion but are independently regulated within a species. Preliminary results from nuclear run-on assays are presented that indicate differences in the level of transcription of the alpha-actin and beta-myosin heavy chain isogenes in the rat heart.

Evidence for expression of a common myosin heavy chain phenotype in future fast and slow skeletal muscle during initial stages of avian embryogenesis

We have utilized a key biochemical determinant of muscle fiber type, myosin isoform expression, to investigate the initial developmental program of future fast and slow skeletal muscle fibers. We examined myosin heavy chain (HC) phenotype from the onset of myogenesis in the limb bud muscle masses of the chick embryo through the differentiation of individual fast and slow muscle masses, as well as in newly formed myotubes generated in adult muscle by weight overload. Myosin HC isoform expression was analyzed by immunofluorescence localization with a battery of anti-myosin antibodies and by electrophoretic separation with SDS-PAGE. Results showed that the initial myosin phenotype in all skeletal muscle cells formed during the embryonic period (until at least 8 days in ovo) consisted of expression of a myosin HC which shares antigenic and electrophoretic migratory properties with ventricular myosin and a distinct myosin HC which shares antigenic and electrophoretic migratory properties with fast skeletal isomyosin. Similar results were observed in newly formed myotubes in adult muscle. Future fast and slow muscle fibers could only be discriminated from each other in developing limb bud muscles by the onset of expression of slow skeletal myosin HC at 6 days in ovo. Slow skeletal myosin HC was expressed only in myotubes which became slow fibers. These findings suggest that the initial commitment of skeletal muscle progenitor cells is to a common skeletal muscle lineage and that commitment to a fiber-specific lineage may not occur until after localization of myogenic cells in appropriate premuscle masses. Thus, the process of localization, or events which occur soon thereafter, may be involved in determining fiber type.

Immunoglobulin heavy chain phenotypes and background retinopathy in non-insulin dependent diabetics.

Etude suivie pendant 10 ans de 110 malades diabetiques, non insulino-dependant. Une correlation significative est trouvee entre le phenotype Gm(zaf; n; bg) et le developpement plus ou moins tardif d'une retinopathie. Cette complication semble dependre d'un composant immunogenetique. La determination du phenotype aiderait a identifier les malades a haut risque de micro-angiopathie

Gm and Km allotypes in rheumatoid arthritis.

Immunoglobulin heavy chain (Gm) and kappa light chain (Km) allotype and phenotype frequencies were compared in 173 patients with rheumatoid arthritis (RA) and in 798 controls. No significant differences were found between allotype or phenotype frequencies in overall RA and control groups. However, the Gm(zaxfngb) phenotype and G1m(x) allotype were increased in HLA-DR4 positive RA patients compared with DR4 negative patients and controls, suggesting that immunoglobulin heavy chain genes interact with HLA in the pathogenesis of RA. All four patients with pulmonary fibrosis were Km(1) positive suggesting a possible role for immunoglobulin kappa light chain genes in the pathogenesis of pulmonary fibrosis found in rheumatoid patients.

Immune phenotype and prognosis in chronic B-lymphocytic leukaemia and leukaemic immunocytoma.

Fifty-nine patients with a leukaemic B-lymphocytic malignancy ("CLL") were studied. According to the Kiel classification, 29 patients had chronic lymphocytic leukaemia (CLL) and 30 had immunocytoma (IC). Cell surface immunoglobulin staining showed mu heavy chain phenotype in 14 patients, mu in 35, gamma in 7; in cells from 3 patients the staining was too weak to permit identification. The light chain phenotype was kappa in 39 patients, lambda in 17, and unidentified in 3. The immunoglobulin isotypes differed between the diagnoses. The gamma chain phenotype was found only in IC patients (p less than 0.02), and more CLL than IC patients showed a lambda chain phenotype (p less than 0.04). Blood lymphocytes from IC patients contained more T cells than CLL cell samples (p less than 0.002). No prognostic difference was found between the CLL and IC group. Compared to the lambda phenotype, the kappa phenotype was associated with a poorer prognosis in the IC group, but with a better prognosis in the CLL group. IC patients with mu phenotype had a poorer prognosis than those with gamma phenotype. Low relative T cell numbers were associated with a poor survival (p less than 0.01).

The incidence of B cell leukaemia and lymphopenia in B cell neoplasia in adults: A study using the Kiel classification of non-Hodgkin's lymphoma

The incidence of B cell leukaemia in 186 consecutive untreated patients with histologically defined B cell neoplasms is described. The lymphomas were classified by the Kiel convention. B cell leukaemia in the context of this paper refers to the situation where a neoplastic clone of B cells in the blood greatly outnumbers normal blood B cells. It is defined as an absolute blood B cell count greater than 0.75 X 10(9)1(-1) where either greater than 90% B cells express kappa immunoglobulin light chains or greater than 80% express lambda light chains. This was found in several patients where the total blood lymphocyte count was within normal limits. All patients with diffuse lymphocytic lymphoma with the histological appearances of B cell chronic lymphocytic leukaemia (ML-BCLL) were found to have B cell leukaemia. However, more than half these patients had blood B cell counts less than 10 X 10(9)1(-1). B cell leukaemia was also a feature in approximately 33% of patients with follicle centre cell tumours and 33% of those with lymphoplasmacytoid tumours. B cell leukaemia was not detected in 34/35 patients with myelomatosis. The 35th patient had plasma cell leukaemia. Only 3/22 patients with high grade lymphoma had B cell leukaemia. In the three principal tumour types associated with B cell leukaemia mu + delta was the most common immunoglobulin heavy chain phenotype. Spontaneous mouse red cell rosette formation also characterised leukaemic B cells in these three groups but high proportions of mouse rosetting cells were seen only in association with ML-BCLL. None of 4 cases of prolymphocytic leukaemia showed mouse red cell rosetting. HLA-DR alpha chain was found on the leukaemic cells of all patients except one with ML-BCLL. B cell lymphopenia was a frequent finding in all histological groups in those patients who did not have B cell leukaemia.

Prognostic Significance of Receptors for the Third Component of Complement and Heavy Chain Phenotype in Diffuse B-Cell Lymphomas

Abstract As part of a larger study to determine the prognostic significance of cell marker phenotype in diffuse lymphomas, 51 patients with monoclonal B-cell lymphoma were further characterized by receptors for C3 (EAC rosettes) as well as heavy and light chain phenotypes. Patients with greater than 10% EAC rosette-forming cells were found to have a statistically significant longer survival than those with less than 10% EAC rosettes (p = 0.005). A similar trend in survival duration was found for patients whose cells expressed mu heavy chain on their surfaces when compared to those with gamma heavy chain on their cell surfaces (p = 0.05). No difference was observed for light chain phenotype. No correlation was observed between these prognostic groups and any of the three most frequently used histologic classifications (i.e., Rappaport, Lukes, Kiel).

Prognostic significance of receptors for the third component of complement an heavy chain phenotype in diffuse B-cell lymphomas

As part of a larger study to determine the prognostic significance of cell marker phenotype in diffuse lymphomas, 51 patients with monoclonal B-cell lymphoma were further characterized by receptors for C3 (EAC rosettes) as well as heavy and light chain phenotypes. Patients with greater than 10% EAC rosette-forming cells were found to have a statistically significant longer survival than those with less than 10% EAC rosettes (p = 0.005). A similar trend in survival duration was found for patients whose cells expressed mu heavy chain on their surfaces when compared to those with gamma heavy chain on their cell surfaces (p = 0.05). No difference was observed for light chain phenotype. No correlation was observed between these prognostic groups and any of the three most frequently used histologic classifications (i.e., Rappaport, Lukes, Kiel).

Genetic factors controlling anti-sheep erythrocyte antibody response and immunoglobulin synthesis in backcross and F2 progeny of mice genetically selected for "high" or "low" antibody synthesis.

Agglutinin responses to sheep erythrocytes and immunoglobulin heavy chain phenotypes determined in F(1), F(2), and backcross progeny of mice genetically selected for high and low antibody synthesis indicated that an immune response gene for sheep erythrocytes is linked to the immunoglobulin heavy chain allotype. Mice homozygous for the phenotype of the high line had significantly higher titers than mice homozygous for the phenotype of the low line. An association was also observed in some progeny of the backcross of the F(1) generation with the low line. However, the control of the immune response was clearly multigenic since heterozygous mice of the same phenotype (2/3, 5) resulting from the two backcrosses (high and low) had very different immune responses. Immunoglobulin levels in the same progeny showed no linkage to the immunoglobulin allotype but a rather simple pattern of inheritance.