Biomedical subjects

F M Hofman

Publications and source records attributed to F M Hofman.

At least 55 records · Page 3Linked to original sources

PubMed1992

Early activation of splenic macrophages by tumor necrosis factor alpha is important in determining the outcome of experimental histoplasmosis in mice.

Experimental infection of animals with Histoplasma capsulatum caused a massive macrophage infiltration into the spleen and induced the production of tumor necrosis factor alpha (TNF-alpha) locally. The cytokine was also produced in vitro by peritoneal exudate macrophages exposed to a large inoculum of yeast cells. Depletion of the cytokine by injection of polyclonal sheep anti-TNF-alpha antibody was detrimental to sublethally infected mice. Fungous burdens in the spleens of TNF-alpha-depleted mice were higher than they were in the infected control mice at days 2, 7, and 9 after infection, and the antibody-treated animals succumbed to the infection. Histopathological study of spleen sections revealed that splenic macrophages were not able to control proliferation of intracellular yeasts as a result of TNF-alpha depletion. It seems that TNF-alpha plays a role in early activation of splenic macrophages which is important in controlling the outcome of an infection.

Animals↗

PubMed1992

Cytokines and immunoregulatory molecules in malignant glial neoplasms.

Cytokines are important regulatory proteins controlling growth and differentiation of normal and malignant glial cells. Astrocytes and microglial cells produce and respond to many of the same cytokines employed by cells of the immune system. The authors have analyzed 15 histologically confirmed malignant glial neoplasms for the presence of infiltrating lymphocytes, macrophages, cytokines, and other immunoregulatory molecules using a panel of specific monoclonal and polyclonal antibodies on frozen-tissue sections. All neoplasms showed focal T-cell infiltration with CD8 cells predominating. Infiltration of activated macrophages (positive for CD11c, class II, and interleukin-2 receptor) was marked in all tumors. Within the neoplasm, tumor necrosis factor-alpha (TNF-alpha)- and interleukin (IL)-6-positive macrophages were prominent in five cases, while the tumor cells themselves were only weakly positive. In the other 10 cases, the numerous infiltrating macrophages were only rarely immunoreactive for TNF-alpha or IL-6. Transforming growth factor-beta (TGF-beta) immunoreactivity was most prominent in those tumors with little TNF-alpha-positive macrophage infiltration, although intratumoral variability was present. This study suggests that, in malignant gliomas, the cytokines TNF-alpha and IL-6, although weakly present in neoplastic cells, are most prominent in infiltrating macrophages and in those regions of the tumors that show little immunoreactivity for TGF-beta. The important interactions among neoplastic, reactive glial, and inflammatory cells, which regulate tumor growth, are likely to be in part mediated through these molecules.

Adult↗

PubMed1992

Tumor necrosis factor-alpha in the retina in acquired immune deficiency syndrome.

The presence of specific cytokines and the number and distribution of leukocytes were determined in the retinas of patients with acquired immune deficiency syndrome (AIDS). Using immunohistocytochemical techniques, three retinas from patients with AIDS had focal infiltration by T-lymphocytes and macrophages. These specimens stained positively for tumor necrosis factor-alpha (TNF-alpha) in cells identified morphologically as macrophages and glial cells and showed prominent reactive gliosis. The retinas from seven other affected patients had minimal leukocytic infiltration and no TNF-alpha reactivity; gliosis was present in only one. The retinas from clinically normal patients without human immunodeficiency virus (HIV) contained no TNF-alpha-positive cells. Using in situ hybridization for HIV, four of five patients with AIDS had rare positive cells. No interferon-gamma was detected in any of the retinal tissues tested. These data suggest a role for TNF-alpha in the development of AIDS-related retinal disease.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Regional distribution of thrombomodulin in human brain.

Thrombomodulin, an integral membrane protein with important anticoagulant properties, was evaluated for its distribution in blood vessels of human brain. Adjacent sections from frozen human brain were stained for von Willebrand Factor (an endothelium marker) or thrombomodulin. The number of thrombomodulin-positive blood vessels was expressed as a percentage of all blood vessels in a specific area. The density ratio was compared among cortical and subcortical regions in the human brain. Our results indicated that thrombomodulin density in neocortex, cerebellum, medulla and hippocampus was similar. There was, however, significantly less thrombomodulin in putamen (P less than 0.01), pons (P less than 0.001) and mesencephalon (P less than 0.001) compared to neocortex. The regional distribution of thrombomodulin may prove to be helpful for understanding the development of thrombotic diseases of the brain.

Adult↗

PubMed1991

Lymphokines and immunoregulatory molecules in subacute sclerosing panencephalitis.

Frozen brain specimens from six patients with subacute sclerosing panencephalitis (SSPE) were analyzed immunohistochemically for the presence of leukocyte subpopulations and specific cytokines. In brain regions demonstrating perivascular cell infiltration and gliosis, CD4 and CD8 positive cells were identified within the brain parenchyma. Cytokine analysis revealed cells staining positively for tumor necrosis factor-alpha and interferon-gamma. These results were similar to those observed in multiple sclerosis (MS) and progressive rubella panencephalitis tissue and were different from other predominantly noninflammatory neurologic diseases and normal controls. Although SSPE and MS differ significantly in their etiology and histopathology, the similarities in leukocyte and cytokine staining patterns suggest a common mechanism of disease progression.

Adolescent↗

PubMed1991

Class II antigen expression by lacrimal epithelial cells. An updated working hypothesis for antigen presentation by epithelial cells.

It has been suggested that aberrant expression of Class II histocompatibility antigens (HLA) is involved in T cell activation and leads to autoimmunity. Although Class II antigen expression was found in various nonlymphoid tissues, including salivary glands, its expression on lacrimal epithelial cells has not been reported. In this study, 12 cadaver lacrimal glands were analyzed for HLA-DR and for the numbers and distributions of T suppressor cells (Ts), T helper cells (Th), B cells, and macrophages. None of these cases exhibited the high numbers of inflammatory cells, tissue damage, and fibrosis characteristic of Sjogren's syndrome. The HLA-DR-positive epithelial cells were detected in ten cases; they represented from less than 1% to more than 70% of the epithelial cells. In these ten positive cases, there were greater numbers of T cells per millimeter squared (229 +/- 94 [mean +/- the standard error of the mean]) than in the two HLA-DR-negative cases (37 +/- 1 [mean +/- range]). Three lacrimal gland specimens tested were negative for immunoglobulin (Ig) G-bearing B cells, and two of the three specimens tested had IgA-bearing cells. Acinar cells were isolated from rat and rabbit lacrimal glands and cultured overnight in serum-free media supplemented with several potential mediators of Class II antigen expression: interferon-gamma, carbachol, or isoproterenol. Freshly isolated cells did not express Class II antigens at detectable levels, but in most experiments, they began to express the antigen even in the absence of putative mediators.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1990

Differential CD3/T cell antigen receptor-mediated IL-2 production in jurkat T cells. Dissociation of IL-2 response from total inositol phosphate and calcium responses.

We used three anti-human anti-CD3 mAb each recognizing different surface CD3 epitopes to differentially perturb the CD3/TCR complex on the surface of Jurkat T cells. In the presence of phorbol ester, these anti-CD3 mAb triggered differential IL-2 production in Jurkat T cells, which could not be explained by differences in kinetics of IL-2 production, by differences in IL-2 adsorption caused by differential surface expression of p55 or p75 IL-2R, by effects on IL-2 secretion rather than actual synthesis, or by differential toxicities of the anti-CD3 mAb to Jurkat cells. In addition, this differential anti-CD3-induced IL-2 production could not be explained by differences in mAb isotype or in avidities of the anti-CD3 mAb for the Jurkat cells. Moreover, anti-CD3 mAb covalently immobilized onto beads also differentially induced IL-2 production in Jurkat cells, suggesting that the differential IL-2 response is not based on differential rates of anti-CD3-induced modulation of Jurkat cell surface CD3. Although differences among the anti-CD3 mAb in the initial rates of binding to Jurkat cell were observed, this was also believed unlikely to explain the differential IL-2 response. Regardless of the anti-CD3 mAb used, anti-CD3-induced total inositol phosphate (IP) production did not necessarily correlate with anti-CD3-induced IL-2 production. Nevertheless, despite the differences among the anti-CD3 mAb in inducing IL-2 production, the calcium responses were grossly similar. Taken together, these observations indicate that CD3/TCR-mediated IL-2 production in Jurkat cells can be dissociated from total IP generation, and the basis of differential CD3/TCR-mediated IL-2 production in these cells does not appear to be at the level of the initial activation-induced calcium response. These studies suggest that the nature of the CD3/TCR ligand (its physical form and/or the specific epitope it perturbs) can either directly influence intracellular events distal to the generation of IP and increase in intracellular free calcium leading to differential IL-2 production or can trigger IP-independent pathways that affect IL-2 production.

Antibodies, Monoclonal↗

PubMed1989

Tumor necrosis factor identified in multiple sclerosis brain.

Frozen brain specimens from patients with multiple sclerosis (MS) and other neurologic diseases were analyzed using immunocytochemical techniques for the presence of TNF. In brain lesions in MS, and subacute sclerosing panencephalitis, TNF+ cells were demonstrated. At the lesion site in MS, TNF+ staining is associated with both astrocytes and macrophages. These observations were not made in Alzheimer's disease or normal brain tissue. The presence of TNF in MS lesions suggests a significant role for cytokines and the immune response in disease progression.

Astrocytes↗

PubMed1989

Lymphocytes bearing antigen-specific gamma delta T-cell receptors accumulate in human infectious disease lesions.

The majority of T cells bear the T-cell receptor (TCR) alpha beta complex which recognizes foreign antigen peptides only in the context of self major histocompatibility complex (MHC) molecules. Such T cells function in a variety of effector roles and secrete cytokines that mediate the activation and differentiation of other cells in the immune system. Recently, a small subpopulation T cells was found to bear a distinct TCR composed of gamma and delta subunits. In man, TCR gamma delta+ cells are distributed as approximately 5 per cent of the CD3+ cells in all organized lymphoid organs as well as in the skin- and gut-associated lymphoid tissues. Although a limited number of germ-line genes encode the TCR gamma and delta subunits, extensive junctional variation particularly in the delta gene, results in unprecedented diversity for this receptor. The nature of the specificity and immunological functions of these T cells remains enigmatic. We report here that in contrast to the normal low frequency of gamma delta-bearing cells in lymphoid tissues, peripheral blood, or normal skin, the frequency is increased five to eightfold in particular granulomatous reactions of leprosy. TCR gamma delta+ lymphocyte lines from these leprosy skin lesions proliferate in vitro specifically to mycobacterial antigens. This reactivity to foreign antigens appears to require presentation in the context of self-molecules. Moreover, culture supernatants from activated gamma delta T lymphocytes induce adhesion and aggregation of bone-marrow monocytes in the presence of granulocyte monocyte-colony stimulating factor (CSF), suggesting that products of gamma delta-bearing T cells may play a role in the immune response, possibly by stimulating granuloma formation.

Epitopes↗

PubMed1989

An immunohistochemical study of the endolymphatic sac in patients with acoustic tumors.

Intraosseous endolymphatic sacs obtained from patients with acoustic neuromas who had undergone total labyrinthectomy during tumor removal were examined for the presence of T helper/inducer and T suppressor/cytotoxic lymphocytes, B lymphocytes, plasma cells, and macrophages. Immunoperoxidase staining of cryostat sections revealed the presence of T helper/inducer lymphocytes, T suppressor/cytotoxic lymphocytes, and macrophages. The number of B lymphocytes and plasma cells was much smaller than the number of T lymphocytes. The number of T suppressor/cytotoxic lymphocytes was higher than the number of T helper/inducer lymphocytes. This study supports the notion of local immune responsiveness in the human inner ear. This is the first immunohistochemical study to analyze lymphocyte subpopulations; specifically, to provide insight into T-cell function in the endolymphatic sac.

Antigens, Differentiation↗

PubMed1988

IL-4 regulates differentiation and proliferation of human precursor B cells.

The mechanism by which precursor and pre-B cells undergo differentiation is unclear; however, it is known that growth factors play an important role in this maturation process. The lymphokine, IL-4 has been shown to increase expression of class II Ag on B cells and induce B cell proliferation. In the murine system, IL-4 induced differentiation of precursor B cells into pre-B cells. In order to analyze growth factors on B cell development we have established an in vitro culture system for human bone marrow cells. We found that in the presence of IL-4, normal human precursor and pre-B cells can be induced to differentiate in the absence of cell proliferation with four days of culture. Furthermore, IL-4 depressed proliferation induced by supernatant from a T cell line. The differentiation was measured by an increase in both the number of cytoplasmic mu and surface IgM-positive cells. The effect of IL-4 on precursor and pre-B cell differentiation was detected as soon as 14 h of exposure to the lymphokine in the absence of an adherent feeder layer. These data suggest that IL-4 directly affects the differentiation process of normal human precursor and pre-B cells, and may antagonistically affect cell proliferation.

Antigens, Differentiation, B-Lymphocyte↗

PubMed1987

Immunohistology of persistent generalized lymphadenopathy. Evidence for progressive lymph node abnormalities in some patients.

Immunohistologic analysis of cellular changes in serial lymph node biopsies of eight patients with persistent generalized lymphadenopathy (PGL) syndrome was performed and correlated with clinical and laboratory findings to better determine the natural history of human immunodeficiency virus (HIV) infection. The authors observed decreased follicle size and area in the second biopsies of six of the eight patients, associated in some with increased numbers of B-cells in medullary regions (four of eight) and more involuted follicles (four of eight). Five cases showed progressively increased paracortical areas in the second biopsies, with increased numbers of T-cytotoxic/suppressor cells and decreased T-helper cells. Seven of the patients also had a progressive loss of T-helper cells in the peripheral blood. These findings provide tissue and peripheral blood evidence for progressive immunologic deterioration in some patients with PGL.

AIDS-Related Complex↗

PubMed1987

In situ identification of activated Ta1+ T lymphocytes in human leprosy skin lesions.

Using a monoclonal antibody, anti-Ta1, that identifies antigen-activated T lymphocytes in vitro, we sought to identify activated T lymphocytes in leprosy skin lesions. Greater numbers of Ta1 positive T lymphocytes were observed in tuberculoid leprosy, lepromin skin tests, and reversal reactions as compared with lepromatous leprosy or erythema nodosum leprosum (ENL) (p less than 0.001). With a double-staining technique, we found that the majority of these activated T lymphocytes were of the helper/inducer phenotype. No differences of Ta1 positive lymphocytes were observed in the peripheral blood. The defective cell-mediated immune response in lepromatous and ENL patients correlates with, and may be related to the failure of T-helper/inducer activation or proliferation in the presence of Mycobacterium leprae.

Antibodies, Monoclonal↗

PubMed1986

Immunoregulatory molecules and IL 2 receptors identified in multiple sclerosis brain.

Frozen brain specimens from eight multiple sclerosis (MS) patients were examined for the presence of leukocytes and their cell products by using a panel of monoclonal antibodies. The results presented here demonstrated that in the MS lesion, there was a marked accumulation of HLA-Dr-positive (Ia-positive) cells. These Ia-positive cells were identified as being glial fibrillary acidic protein positive by using double staining methods. Furthermore, the cells in the MS lesion expressed the interleukin 2 (IL 2) receptor, as identified by the anti-TAC monoclonal antibody. The cells in the region of the plaque also exhibited positive staining with antibodies to IL 1, IL 2, and prostaglandin E. Neither normal brain nor brain specimens from progressive multifocal leukoencephalopathy or Alzheimer's disease showed such patterns of staining. These results suggest that stimulated cells are present in the MS brain, thus implicating an active immune mechanism in the pathogenesis of MS.

Adolescent↗

PubMed1986

The differentiation antigens of macrophages in human fetal liver.

Macrophage populations from human fetal liver were examined for the sequential appearance of different antigenic determinant during maturation. Frozen sections of liver, from 12 to 21 weeks gestation were analyzed using a series of four monoclonal antibodies with known specificity. The macrophage monoclonal antibodies used were OKM-1, which defines monocytes, macrophages, and granulocytes; Leu M-3 and MO-2, which identify monocytes and macrophages; and 6B8, a new macrophage monoclonal antibody which binds to tissue macrophages. The staining pattern described by each of these monoclonal reagents was compared with the distribution of morphologically distinguishable tissue macrophages in fetal liver, based on the expression of surface and/or cytoplasmic antigens. The data indicate that the antigens defined by OKM-1 and 6B8 are present on large numbers of cells as early as 12 weeks gestation. In contrast, the antigenic determinants identified by Leu M-3 and MO-2 are present only on cells in 15 to 21 weeks of gestation; thus these antigens are mature differentiation antigens. Furthermore, double-staining studies confirmed that with the increase in fetal age unique macrophage populations can be identified based on the matrix of antigenic determinants. Thus, macrophage heterogeneity in the fetal liver may be a function of maturation.

Antibodies, Monoclonal↗

PubMed1985

B- and T-lymphocytes in Hodgkin's disease. An immunohistochemical study utilizing heterologous and monoclonal antibodies.

Immunohistologic techniques utilizing monoclonal antibodies have made possible the identification of leukocytes by their phenotypic characteristics rather than by morphologic features alone. A panel of antibodies for T-lymphocyte, B-lymphocyte, and monocyte/histiocyte markers has been applied to frozen sections of nodular sclerosing and mixed cellularity Hodgkin's disease to identify more precisely the various cell types present in tissues involved in Hodgkin's disease. The majority of lymphocytes expressed detectable T-cell phenotypic markers, with a predominance of the "helper" phenotype (Leu 3/OKT4) in most cases. Lymphocytes reacting with anti-B-cell antibodies were also demonstrated; their distribution is described here and has not previously been reported. The anti-B- and anti-T-cell antibodies used in this study failed to give positive reactivity with Reed-Sternberg cells. However, one of the anti-monocyte antibodies (Leu-M1) reacted with diagnostic Reed-Sternberg cells in some cases. The patterns of staining observed varied widely within the two histologic types of Hodgkin's disease, leading to a conclusion that this disease may be more heterogeneous than is currently suspected.

Antibodies, Monoclonal↗

PubMed1985

Primary central nervous system lymphoma in homosexual men. Clinical, immunologic, and pathologic features.

Primary central nervous system lymphoma constitutes one of the criteria for the acquired immune deficiency syndrome (AIDS), yet a paucity of information is currently available regarding the clinical, immunologic, or pathologic features of these patients. Six homosexual men presenting with primary central nervous system lymphoma were evaluated. Five of these patients presented with altered mental status. All lymphomas were intracranial. B cell immunoblastic sarcoma was found in five. Immune phenotyping studies performed in five patients revealed monoclonal lambda light chain in three, whereas one expressed only IgG heavy chain, and one demonstrated another B cell (LN-1) surface antigen. Hypodense, contrast-enhancing lesions were apparent on computed axial tomographic scanning of the brain, in sharp contrast to isodense or hyperdense lesions reported in primary central nervous system lymphomas without underlying immunodeficiency. Immunologic abnormalities in these patients were similar to those in AIDS presenting as Kaposi's sarcoma or with opportunistic infections. In spite of therapeutic interventions, survival was short, and only one patient is currently alive.

Adult↗

PubMed1985

In situ localization of T lymphocytes in disseminated coccidioidomycosis.

Immunohistochemical techniques using monoclonal antibodies to T lymphocyte subpopulations were used to characterize further the granulomas of disseminated coccidioidomycosis. Skin biopsy specimens from patients with disseminated coccidioidomycosis were studied and compared with tissues from experimentally infected mice. In human skin biopsy specimens and infected mouse tissues, discrete granulomata were seen in which T lymphocytes formed a peripheral mantle surrounding central aggregates of macrophages. This unusual pattern of granuloma formation may represent an ineffective host response because these individuals are unable to clear their infection. Because of the close similarity of immunopathology in both human and mouse infections, the mouse model should serve as a useful tool in elucidating the factors contributing to ineffective host responses in systemic fungal infections.

Adolescent↗