Frederick Siegal - Academia.edu (original) (raw)
Papers by Frederick Siegal
The American Journal of Cardiology, 2003
Short-term effect of atorvastatin (80 mg) on plasma lipids of patients with unstable angina pecto... more Short-term effect of atorvastatin (80 mg) on plasma lipids of patients with unstable angina pectoris or non-Q-wave acute myocardial infarction.
SUMMARY Theresponses offresh andfrozen lymphocytes tomitogens andantigens havebeencompared using ... more SUMMARY Theresponses offresh andfrozen lymphocytes tomitogens andantigens havebeencompared using samples collected onfive separate occasions fromonenormal donor. Theday-to-day variation seenwith thefresh cells waseliminated bytheuseoffrozen cells. Thawedcells from onedonor collected ononeoccasion butstudied onfive separate occasions andcompared tofresh cells onthesamedays, showed fluctuations fromdaytodayaswell, confirming that theday-todayvariation seenisduetotechnical andnotbiological phenomena. Cryopreserved cells showed a decrease inresponses tospecific microbial antigens, aslight shift inthePHAdose-response curve, butnosignificant difference inresponses toConAorPWM.Therelative proportion of lymphocyte subpopulations changed with freezing andthawing. Theproportion ofT cells increased slightly andtheproportion ofBcells decreased.
Clinics in Haematology, 1977
The study of human lymphoid cell differentiation markers has recently yielded many insights into ... more The study of human lymphoid cell differentiation markers has recently yielded many insights into the pathogenesis of certain diseases which primarily affect the immune system. The application of these markers has, however, generated a host of new questions. Both technical difficulties and uncertainties concerning the significance of particular markers limit their routine application at the present time. Indeed, many studies in the literature, both in the diseases reviewed above, and perhaps to a greater degree in other conditions ('autoimmune' diseases, sarcoidosis, hepatitis and various infections) require re-evaluation in the light of recently increased sophistication about cell surfaces. Because of these qualificatins, the application of multiple characterizations of lymphoid cells using independent methodologies is necessary before any firm conclusions can be drawn in a particular clinical or experimental situation.
Blood, 1987
Patients infected with the human immunodeficiency virus (HIV) often present with neutropenia. To ... more Patients infected with the human immunodeficiency virus (HIV) often present with neutropenia. To elucidate the mechanism(s) of this HIV- related neutropenia, we assessed the proliferative capacity of the granulocyte-macrophage progenitor cell (CFU-GM) from the bone marrow (BM) of 78 patients within the AIDS spectrum manifesting symptoms or signs related to HIV infection. Of these, 70 had a significant deficit in the growth of this committed progenitor when compared with normal controls (P less than .01). Further analysis revealed that the nucleated bone marrow cells from AIDS and AIDS-related complex (ARC) patients inhibited the growth of CFU-GMs from normal individuals when cocultured in agar (P less than .001). Control CFU-GMs were also inhibited when they were cultured over feeder layers containing…
Blood, 1977
Leukemic cells from nine cases of acute monocytic leukemia (AMoL) were characterized by multiple ... more Leukemic cells from nine cases of acute monocytic leukemia (AMoL) were characterized by multiple differentiation markers. Cells in most cases were phagocytic, carried an Fc receptor, and stained positively for alpha-naphthyl acetate esterase but negatively for naphthol AS-D chloroacetate esterase. However, subtle differences in marker expression were observed which suggested different degrees of leukemic cellular maturation or activation. Cell marker analysis proved to be a useful adjunct to conventional morphology in confirming the diagnosis and the recognition of the neoplastic cells in AMoL, and may ultimately provide insight into the functional state of these cells.
Clinical Immunology and Immunopathology, 1974
The effect of thymus extract on the development of cell surface antigenicity in two patients with... more The effect of thymus extract on the development of cell surface antigenicity in two patients with primary immunodeficiency was studied and compared. A stem cell fraction from bone marrow preparations of a patient with severe combined immunodeficiency failed to develop cells with antigenic markers of T-lymphocytes while that of a patient with common variable form of immunodeficiency who had both severe functional deficits of T-lymphocytes and agammaglobulinemia developed cells with such markers after treatment with thymus extract. These findings indicate that the two forms of severe combined immunodeficiency disease studied have different bases which may be reflected in differences of response to differentiative influence of thymus extract.
J Allerg Clin Immunol, 2001
Clinical & Experimental Immunology
ABSTRACT
Mount Sinai Journal of Medicine A Journal of Translational and Personalized Medicine
Nemaline-rod myopathy was recently reported in eight young males infected with human immune defic... more Nemaline-rod myopathy was recently reported in eight young males infected with human immune deficiency virus type 1 (HIV-1). A 41-year-old woman had a 2-year history of progressive proximal-muscle weakness. Muscle biopsy demonstrated the presence of nemaline rods, predominantly in type 1 fibers. She was coinfected with HIV-1 and HTLV-2, as evidenced by positive polymerase chain reaction and serology. There was no lymphopenia or CD4 lymphopenia, despite an abnormal T-cell subset ratio, high CD8 count, skin anergy, and depressed in vitro response to mitogens. This case raises the possibility that dual infection may play a role in the pathogenesis of the rare nemaline-rod myopathies of HIV-infected patients.
Birth defects original article series, 1983
Journal of acquired immune deficiency syndromes, 1993
We have previously demonstrated that in vitro production of interferon-alpha (IFN-alpha) in respo... more We have previously demonstrated that in vitro production of interferon-alpha (IFN-alpha) in response to herpes simplex virus (HSV) by peripheral blood mononuclear cells PBMCs from patients infected with the human immunodeficiency virus (HIV-1) decreases dramatically with disease progression, with extremely low levels of IFN-alpha preceding and predictive of opportunistic infections. Natural killer (NK) lysis, however, was found to decay later in disease and often was within normal limits even when IFN-alpha production was severely compromised. The NK lysis of HSV-infected fibroblasts (HSV-FS) is dependent on an HLA-DR+ accessory cell (AC) population that shares the phenotype of the predominant IFN-alpha-producing cell (IPC) population. To determine whether there is a correlation between AC activity and IFN-alpha production in these patients, we tested the ability of PBMCs from AIDS patients to provide AC help to NK cells from heterologous donors. While NK cells were highly sensitive...
Leukemia, 1994
Patients with hairy cell leukemia (HCL) are susceptible to opportunistic intracellular infections... more Patients with hairy cell leukemia (HCL) are susceptible to opportunistic intracellular infections, suggesting defects in cellular immunity. Prior studies have indicated an association between failure of IFN-alpha generation by peripheral blood mononuclear cells (MNC) and susceptibility to such infections. We here present results on IFN-alpha generation in HCL patients pre- and post-therapy. Prior to treatment with 2-chloro-2'-deoxyadenosine (CdA), MNC from 24 HCL patients with active disease produced little or not IFN-alpha (geometric mean < 40 IU/ml) compared with controls (n = 140, geometric mean 1730 IU/ml, p < 0.0005). After treatment with CdA, IFN-alpha generation was studied in 16 patients, with a geometric mean value of 650 IU/ml (p < 0.0005 compared with pre-CdA levels). The severe depression of IFN-alpha generation improved progressively following CdA therapy-induced clinical remission. We propose that deficiency of IFN-alpha production may play a role in the s...
Journal of immunology (Baltimore, Md. : 1950), 1982
Leukemic cells from a patient with an 11-yr history of chronic lymphocytic leukemia (CLL) were fo... more Leukemic cells from a patient with an 11-yr history of chronic lymphocytic leukemia (CLL) were found to have the surface phenotype Leu-1+, Leu-2a+, Leu-3a-, sheep erythrocyte rosette+, IgGFc receptor+. The cells also bore a receptor for histamine inhibitable by cimetidine (H-2). The clonal nature of the proliferation was documented by the presence of a consistent marker chromosome (22-trisomy) in metaphases elicited by culture with T cell growth factors. Although the surface phenotype suggested that these cells might function as suppressor lymphocytes, they had an enhancing effect on the pokeweed- mitogen- (PWM) driven generation of plasma cells and reverse hemolytic plaque-forming cells in vitro. This helper activity was modified neither by irradiation of the leukemic cells nor by removal of a minor population of Leu-3a+ cells, suggesting that the effects were attributable to the CLL cells themselves. In addition to these functions, the CLL cells were active in antibody-dependent c...
Transactions of the Association of American Physicians, 1974
Archives of pathology & laboratory medicine, 1985
Bone marrow biopsies from 30 patients with acquired immunodeficiency syndrome (AIDS), diagnosed a... more Bone marrow biopsies from 30 patients with acquired immunodeficiency syndrome (AIDS), diagnosed according to accepted clinical criteria, were studied in order to determine if characteristic histopathologic features were present. The biopsies were compared with 20 biopsy specimens submitted from patients with fever of unknown origin or with known neoplastic disease, including four biopsies from patients with a history of narcotics addiction being treated in the methadone clinic, and with biopsies from three homosexual men who did not have AIDS. Characteristic biopsy features were recognized in 31 (86%) of 36 biopsy specimens from AIDS patients. Nineteen of 36 patients (53%) showed a distinctive pattern of hypercellularity in which hematic cells (immature granulocytic cells, megakaryocytes, eosinophils, and large lymphocytes) separated, but did not efface, fat cells; these cells were designated as "AIDS-pattern." Twelve specimens showed a less complete (probable-AIDS) bone m...
Clinical and experimental immunology, 1976
The responses of fresh and frozen lymphocytes to mitogens and antigens have been compared using s... more The responses of fresh and frozen lymphocytes to mitogens and antigens have been compared using samples collected on five separate occasions from one normal donor. The day-to-day variation seen with the fresh cells was eliminated by the use of frozen cells. Thawed cells from one donor collected on one occasion but studied on five separate occasions and compared to fresh cells on the same days, showed fluctuations from day to day as well, confirming that the day-to-day variation seen is due to technical and not biological phenomena. Cryopreserved cells showed a decrease in responses to specific microbial antigens, a slight shift in the PHA dose-response curve, but no significant difference in responses to Con A or PWM. The relative proportion of lymphocyte subpopulations changed with freezing and thawing. The proportion of T cells increased slightly and the proportion of B cells decreased.
Clinical and experimental immunology, 1976
Peripheral blood lymphocytes from healthy control subjects were studied for spontaneous rosette-f... more Peripheral blood lymphocytes from healthy control subjects were studied for spontaneous rosette-formation with mouse erythrocytes. The mean percentage of mouse erythrocyte rosette-forming cells (MRFC) in sixty-three subjects was 7.4X3.5; after neuraminidase treatment olymphocytes the mean percentage of mouse erythrocyte rosette-forming cells(NMRFC) was 17.2X5.6. Thymus cell suspensions made only occasional rosettes with mouse erythrocytes. There was no effect of neuraminidase treatment of thymocytes on mouse erythrocyte rosette-formation. Double labelling experiments with other cell surface markers confirmed this binding of mouse erythrocytes to be a B-cell characteristic. Monocytes and granulocytes do not bind mouse erythrocytes. It appears that there is a distinct receptor for the binding of mouse erythrocytes on the surface of lymphocytes carrying surface immunoglobulins; neuraminidase treatment of lymphocytes permits this binding to occur also on virtually all the non-T cells B ...
The American Journal of Cardiology, 2003
Short-term effect of atorvastatin (80 mg) on plasma lipids of patients with unstable angina pecto... more Short-term effect of atorvastatin (80 mg) on plasma lipids of patients with unstable angina pectoris or non-Q-wave acute myocardial infarction.
SUMMARY Theresponses offresh andfrozen lymphocytes tomitogens andantigens havebeencompared using ... more SUMMARY Theresponses offresh andfrozen lymphocytes tomitogens andantigens havebeencompared using samples collected onfive separate occasions fromonenormal donor. Theday-to-day variation seenwith thefresh cells waseliminated bytheuseoffrozen cells. Thawedcells from onedonor collected ononeoccasion butstudied onfive separate occasions andcompared tofresh cells onthesamedays, showed fluctuations fromdaytodayaswell, confirming that theday-todayvariation seenisduetotechnical andnotbiological phenomena. Cryopreserved cells showed a decrease inresponses tospecific microbial antigens, aslight shift inthePHAdose-response curve, butnosignificant difference inresponses toConAorPWM.Therelative proportion of lymphocyte subpopulations changed with freezing andthawing. Theproportion ofT cells increased slightly andtheproportion ofBcells decreased.
Clinics in Haematology, 1977
The study of human lymphoid cell differentiation markers has recently yielded many insights into ... more The study of human lymphoid cell differentiation markers has recently yielded many insights into the pathogenesis of certain diseases which primarily affect the immune system. The application of these markers has, however, generated a host of new questions. Both technical difficulties and uncertainties concerning the significance of particular markers limit their routine application at the present time. Indeed, many studies in the literature, both in the diseases reviewed above, and perhaps to a greater degree in other conditions (&amp;#39;autoimmune&amp;#39; diseases, sarcoidosis, hepatitis and various infections) require re-evaluation in the light of recently increased sophistication about cell surfaces. Because of these qualificatins, the application of multiple characterizations of lymphoid cells using independent methodologies is necessary before any firm conclusions can be drawn in a particular clinical or experimental situation.
Blood, 1987
Patients infected with the human immunodeficiency virus (HIV) often present with neutropenia. To ... more Patients infected with the human immunodeficiency virus (HIV) often present with neutropenia. To elucidate the mechanism(s) of this HIV- related neutropenia, we assessed the proliferative capacity of the granulocyte-macrophage progenitor cell (CFU-GM) from the bone marrow (BM) of 78 patients within the AIDS spectrum manifesting symptoms or signs related to HIV infection. Of these, 70 had a significant deficit in the growth of this committed progenitor when compared with normal controls (P less than .01). Further analysis revealed that the nucleated bone marrow cells from AIDS and AIDS-related complex (ARC) patients inhibited the growth of CFU-GMs from normal individuals when cocultured in agar (P less than .001). Control CFU-GMs were also inhibited when they were cultured over feeder layers containing…
Blood, 1977
Leukemic cells from nine cases of acute monocytic leukemia (AMoL) were characterized by multiple ... more Leukemic cells from nine cases of acute monocytic leukemia (AMoL) were characterized by multiple differentiation markers. Cells in most cases were phagocytic, carried an Fc receptor, and stained positively for alpha-naphthyl acetate esterase but negatively for naphthol AS-D chloroacetate esterase. However, subtle differences in marker expression were observed which suggested different degrees of leukemic cellular maturation or activation. Cell marker analysis proved to be a useful adjunct to conventional morphology in confirming the diagnosis and the recognition of the neoplastic cells in AMoL, and may ultimately provide insight into the functional state of these cells.
Clinical Immunology and Immunopathology, 1974
The effect of thymus extract on the development of cell surface antigenicity in two patients with... more The effect of thymus extract on the development of cell surface antigenicity in two patients with primary immunodeficiency was studied and compared. A stem cell fraction from bone marrow preparations of a patient with severe combined immunodeficiency failed to develop cells with antigenic markers of T-lymphocytes while that of a patient with common variable form of immunodeficiency who had both severe functional deficits of T-lymphocytes and agammaglobulinemia developed cells with such markers after treatment with thymus extract. These findings indicate that the two forms of severe combined immunodeficiency disease studied have different bases which may be reflected in differences of response to differentiative influence of thymus extract.
J Allerg Clin Immunol, 2001
Clinical & Experimental Immunology
ABSTRACT
Mount Sinai Journal of Medicine A Journal of Translational and Personalized Medicine
Nemaline-rod myopathy was recently reported in eight young males infected with human immune defic... more Nemaline-rod myopathy was recently reported in eight young males infected with human immune deficiency virus type 1 (HIV-1). A 41-year-old woman had a 2-year history of progressive proximal-muscle weakness. Muscle biopsy demonstrated the presence of nemaline rods, predominantly in type 1 fibers. She was coinfected with HIV-1 and HTLV-2, as evidenced by positive polymerase chain reaction and serology. There was no lymphopenia or CD4 lymphopenia, despite an abnormal T-cell subset ratio, high CD8 count, skin anergy, and depressed in vitro response to mitogens. This case raises the possibility that dual infection may play a role in the pathogenesis of the rare nemaline-rod myopathies of HIV-infected patients.
Birth defects original article series, 1983
Journal of acquired immune deficiency syndromes, 1993
We have previously demonstrated that in vitro production of interferon-alpha (IFN-alpha) in respo... more We have previously demonstrated that in vitro production of interferon-alpha (IFN-alpha) in response to herpes simplex virus (HSV) by peripheral blood mononuclear cells PBMCs from patients infected with the human immunodeficiency virus (HIV-1) decreases dramatically with disease progression, with extremely low levels of IFN-alpha preceding and predictive of opportunistic infections. Natural killer (NK) lysis, however, was found to decay later in disease and often was within normal limits even when IFN-alpha production was severely compromised. The NK lysis of HSV-infected fibroblasts (HSV-FS) is dependent on an HLA-DR+ accessory cell (AC) population that shares the phenotype of the predominant IFN-alpha-producing cell (IPC) population. To determine whether there is a correlation between AC activity and IFN-alpha production in these patients, we tested the ability of PBMCs from AIDS patients to provide AC help to NK cells from heterologous donors. While NK cells were highly sensitive...
Leukemia, 1994
Patients with hairy cell leukemia (HCL) are susceptible to opportunistic intracellular infections... more Patients with hairy cell leukemia (HCL) are susceptible to opportunistic intracellular infections, suggesting defects in cellular immunity. Prior studies have indicated an association between failure of IFN-alpha generation by peripheral blood mononuclear cells (MNC) and susceptibility to such infections. We here present results on IFN-alpha generation in HCL patients pre- and post-therapy. Prior to treatment with 2-chloro-2'-deoxyadenosine (CdA), MNC from 24 HCL patients with active disease produced little or not IFN-alpha (geometric mean < 40 IU/ml) compared with controls (n = 140, geometric mean 1730 IU/ml, p < 0.0005). After treatment with CdA, IFN-alpha generation was studied in 16 patients, with a geometric mean value of 650 IU/ml (p < 0.0005 compared with pre-CdA levels). The severe depression of IFN-alpha generation improved progressively following CdA therapy-induced clinical remission. We propose that deficiency of IFN-alpha production may play a role in the s...
Journal of immunology (Baltimore, Md. : 1950), 1982
Leukemic cells from a patient with an 11-yr history of chronic lymphocytic leukemia (CLL) were fo... more Leukemic cells from a patient with an 11-yr history of chronic lymphocytic leukemia (CLL) were found to have the surface phenotype Leu-1+, Leu-2a+, Leu-3a-, sheep erythrocyte rosette+, IgGFc receptor+. The cells also bore a receptor for histamine inhibitable by cimetidine (H-2). The clonal nature of the proliferation was documented by the presence of a consistent marker chromosome (22-trisomy) in metaphases elicited by culture with T cell growth factors. Although the surface phenotype suggested that these cells might function as suppressor lymphocytes, they had an enhancing effect on the pokeweed- mitogen- (PWM) driven generation of plasma cells and reverse hemolytic plaque-forming cells in vitro. This helper activity was modified neither by irradiation of the leukemic cells nor by removal of a minor population of Leu-3a+ cells, suggesting that the effects were attributable to the CLL cells themselves. In addition to these functions, the CLL cells were active in antibody-dependent c...
Transactions of the Association of American Physicians, 1974
Archives of pathology & laboratory medicine, 1985
Bone marrow biopsies from 30 patients with acquired immunodeficiency syndrome (AIDS), diagnosed a... more Bone marrow biopsies from 30 patients with acquired immunodeficiency syndrome (AIDS), diagnosed according to accepted clinical criteria, were studied in order to determine if characteristic histopathologic features were present. The biopsies were compared with 20 biopsy specimens submitted from patients with fever of unknown origin or with known neoplastic disease, including four biopsies from patients with a history of narcotics addiction being treated in the methadone clinic, and with biopsies from three homosexual men who did not have AIDS. Characteristic biopsy features were recognized in 31 (86%) of 36 biopsy specimens from AIDS patients. Nineteen of 36 patients (53%) showed a distinctive pattern of hypercellularity in which hematic cells (immature granulocytic cells, megakaryocytes, eosinophils, and large lymphocytes) separated, but did not efface, fat cells; these cells were designated as "AIDS-pattern." Twelve specimens showed a less complete (probable-AIDS) bone m...
Clinical and experimental immunology, 1976
The responses of fresh and frozen lymphocytes to mitogens and antigens have been compared using s... more The responses of fresh and frozen lymphocytes to mitogens and antigens have been compared using samples collected on five separate occasions from one normal donor. The day-to-day variation seen with the fresh cells was eliminated by the use of frozen cells. Thawed cells from one donor collected on one occasion but studied on five separate occasions and compared to fresh cells on the same days, showed fluctuations from day to day as well, confirming that the day-to-day variation seen is due to technical and not biological phenomena. Cryopreserved cells showed a decrease in responses to specific microbial antigens, a slight shift in the PHA dose-response curve, but no significant difference in responses to Con A or PWM. The relative proportion of lymphocyte subpopulations changed with freezing and thawing. The proportion of T cells increased slightly and the proportion of B cells decreased.
Clinical and experimental immunology, 1976
Peripheral blood lymphocytes from healthy control subjects were studied for spontaneous rosette-f... more Peripheral blood lymphocytes from healthy control subjects were studied for spontaneous rosette-formation with mouse erythrocytes. The mean percentage of mouse erythrocyte rosette-forming cells (MRFC) in sixty-three subjects was 7.4X3.5; after neuraminidase treatment olymphocytes the mean percentage of mouse erythrocyte rosette-forming cells(NMRFC) was 17.2X5.6. Thymus cell suspensions made only occasional rosettes with mouse erythrocytes. There was no effect of neuraminidase treatment of thymocytes on mouse erythrocyte rosette-formation. Double labelling experiments with other cell surface markers confirmed this binding of mouse erythrocytes to be a B-cell characteristic. Monocytes and granulocytes do not bind mouse erythrocytes. It appears that there is a distinct receptor for the binding of mouse erythrocytes on the surface of lymphocytes carrying surface immunoglobulins; neuraminidase treatment of lymphocytes permits this binding to occur also on virtually all the non-T cells B ...