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S Jalkanen

Publications and source records attributed to S Jalkanen.

At least 109 records · Page 6Linked to original sources
PubMed1991

Intracellular pathogens and professional phagocytes in reactive arthritis.

Reactive arthritis is a postinfectious complication which develops after certain infections, mostly gastrointestinal or urogenital. Antigenic structures of the causative microbes, but no live organisms, have been demonstrated in inflamed joints. The host factors as well as the microbial antigens responsible for the initiation of the arthritic process are unknown. The pathogenesis of reactive arthritis is discussed here with special reference to the intracellular life of the causative microbes and to monocytes/macrophages, which may be involved in early events of the arthritic process as well as in maintenance of the autoimmune type of responses.

Antigens, Bacterial↗
PubMed1991

Lymphocyte homing and clinical behavior of non-Hodgkin's lymphoma.

Lymphocyte homing receptors (HRs) defined by Hermes antibodies (anti-CD44) and lymphocyte function associated antigen-1 (LFA-1, CD11a/CD18) are involved in lymphocyte binding to endothelial cells of high endothelial venules (HEVs) at sites where lymphocytes exit the blood. Their expression was correlated to the clinical behavior of 245 non-Hodgkin's lymphomas followed up for the median of 87 mo after the diagnosis. Lymphomas that showed no or weak staining intensity for HRs were more often of stage I (P = 0.005), disseminated less frequently hematogenously (P = 0.003), and had more favorable prognosis than lymphomas with intensive staining for HRs (P less than 0.0001) despite that they were more often histologically of high grade malignancy (P = 0.002). Expression of LFA-1 beta chain (CD18) did not correlate significantly with stage or survival, but had prognostic value in a subgroup of HR expression negative lymphomas (P = 0.03). HR staining intensity was an independent prognostic factor in a multivariate analysis. These findings indicate that Hermes/CD44 molecule is associated to the determination of the metastatic potential and prognosis of non-Hodgkin's lymphomas. They also reveal a new entity among non-Hodgkin's lymphomas, because lymphomas that express low levels of HR have favorable prognosis despite their often highly malignant histological appearance.

Adolescent↗
PubMed1991

Regulation of lymphocyte traffic to mucosa-associated lymphatic tissues.

Lymphocyte recognition and binding to endothelial cells at sites where lymphocytes exit the blood is controlled by several molecules. At mucosal sites, the lymphocytes use at least VLA-4, CD44, and LFA-1 (CD18/CD11a) to bind the endothelial cell ligand molecules. The endothelial cell surface ligand for CD44 is probably a human equivalent of MECA-367 and hyaluronate. LFA-1 can bind to ICAM-1/ICAM-2; and VLA-4, to VCAM-1 on endothelium. However, for physiologic lymphocyte migration, these molecules may still need additional ligands that are currently uncharacterized. At sites of inflammation, cytokines increase the expression of ICAM-1, VCAM-1, and a third endothelial cell antigen, ELAM-1, whose counter-receptor on leukocyte surface is presently unknown. Upregulation of these molecules apparently facilitates the traffic of lymphocytes and other leukocytes to sites of inflammation, thus partially determining the nature and extent of inflammation. These same molecules may be equally responsible for the pathologic characteristics of the immune response seen, for example, in inflammatory bowel diseases.

Animals↗
PubMed1990

Bursectomy of chicken embryos at 60 hours of incubation leads to an oligoclonal B cell compartment and restricted Ig diversity.

Chickens that have been surgically bursectomized at 60 h of embryonic development usually generate Ig producing B cells; however, the bursectomized chickens are incapable of specific antibody responses, even after repeated immunization. In the present work, we analyzed the molecular basis of this immunodeficiency. In the bursectomized chickens, DNA sequencing revealed a repertoire of Ig L and H chains with a low number of different V-J and V-D-J joints, indicating an oligoclonal B cell compartment. In addition, the L and H chains belonging to each B cell clone had similar gene conversion events in the V region. In situ hybridization to Harderian gland tissue sections showed, that B cells of the bursectomized chickens were, however, capable of terminal plasma cell maturation. Thus, in chickens that were lacking the bursal microenvironment, 1) only a few B cell precursors differentiated into mature Ig-producing B cells, 2) low rate of gene conversion resulted in restricted Ig diversity. Regarding the chicken B cell differentiation, the present data support a model that the induction of B cell differentiation is a bursa-independent event, whereas the bursa of Fabricius has a crucial role in the amplification and diversification of the embryonic B cell repertoire.

Amino Acid Sequence↗
PubMed1990

Biologic progression in non-Hodgkin's lymphoma. A flow cytometric study.

The nuclear DNA content of 37 primary non-Hodgkin's lymphomas both at presentation and at relapse was determined by flow cytometric analysis from paraffin-embedded tissue to investigate changes in DNA ploidy and S-phase fraction (SPF) during the course of the disease, and their association with survival. The repeat biopsies were done from 5 months to 15 years after the diagnosis. Four low-grade lymphomas according to the Working Formulation transformed into intermediate-grade lymphomas (four of 11, 36%), and four intermediate-grade lymphomas into high-grade lymphomas during the follow-up (four of 16, 25%), and five of these eight transformed lymphomas were fatal within 18 months after relapse. The SPF correlated strongly with poor prognosis if measured either from the primary biopsy (P = 0.008), the first (P = 0.009), or the latest repeat biopsy (P = 0.006). If SPF was greater than or equal to 6% larger in a repeat biopsy than at presentation prognosis was poor; six of nine such patients died from lymphoma within 11 months from recurrence. An increase of greater than or equal to 6% in the SPF was more common in high-grade (four of nine, 44%) and intermediate-grade (four of 16, 25%) lymphomas than in low-grade lymphomas (one of 11, 9%), and it was occasionally (three of nine) associated with a morphologic change. In a few cases a repeat biopsy was diploid despite DNA aneuploidy at presentation. In conclusion, the study provides evidence that not only may low-grade lymphomas transform into higher grade lymphomas, but high-grade lymphomas may also frequently transform into more malignant forms during the course of the disease. The SPF is useful in monitoring the biological behavior of non-Hodgkin's lymphoma, and it appears to give information not obtained by histologic study alone.

Adult↗
PubMed1990

Prognostic value of lymphocyte homing receptor and S phase fraction in non-Hodgkin's lymphoma.

Lymphocyte homing receptors (HRs) mediate lymphocyte binding to high endothelial venules, and control their circulation between the blood and the lymphoid organs. The role of HRs and nuclear DNA content in the spread and prognosis of non-Hodgkin's lymphoma was studied from paraffin-embedded tumor sections of 104 patients followed-up for the minimum of 5 years after the diagnosis. HR expression was analyzed by staining with a monoclonal antibody, Hermes-3, and DNA content by flow cytometry. Ten (10%) lymphomas were HR negative (HR-), 14 (13%) weakly (HR+/-), and 80 (77%) strongly positive (HR+). HR- lymphomas disseminated less often than HR+/- or HR+ lymphomas (P = .03), and their prognosis was more favorable (P = .03), although they often had a large S phase fraction (SPF), indicating a rapid proliferation rate. A large SPF (greater than 12%) was strongly associated with an unfavorable histologic type in Working Formulation (P = .0001) and poor survival (P = .006), whereas DNA aneuploidy was not. The 5-year survival rate corrected for intercurrent deaths was 61% in lymphomas with SPF less than 12% or with HR-, but only 15% if SPF was greater than 12% and HR+ (P less than .0001). In multivariate analysis stage (P less than .001), SPF (P = .002) and HR (P = .003) were the only independent prognostic factors.

Adult↗
PubMed1990

Salmonella lipopolysaccharide in synovial cells from patients with reactive arthritis.

Synovial cells from nine patients with reactive arthritis following Salmonella enteritidis or Salmonella typhimurium infection were examined for salmonella antigens. Extensive bacterial cultures of the synovial fluid were negative. Eight synovial-fluid cell samples stained positively on immunofluorescence with rabbit antisera against heat-killed S enteritidis or S typhimurium or with monoclonal antibodies specific for the causative salmonella lipopolysaccharide (LPS). Synovial tissue from the ninth patient stained positively in the avidin-biotin-peroxidase complex method with the monoclonal antibody. Control samples (synovial-fluid cells from thirteen patients with other rheumatic diseases and synovial tissue from two) were negative. Synovial cells from eight patients and five controls were studied by western blotting with the same monoclonal antibodies. Four of the eight patients but no controls had blots indicating salmonella LPS in the synovial cells. The presence of bacterial LPS in the joint is a common and pathogenetically important feature of reactive arthritis.

Acute Disease↗
PubMed1990

Nurse cells of the bursa of Fabricius: do they exist?

Cell-cell interactions in B lymphocyte development have so far been incompletely characterized, mostly due to lack of a special organ for B cell maturation in the mammalian species. Certain well-known lymphostromal interactions in the thymus have raised the question whether similar interactions with nurse cells would also operate in the development of B cells. We have tested this hypothesis in the chicken bursa of Fabricius, an organ specific for the B cell maturation. To identify possible nurse cells, with viable lymphocytes enclosed, the cells in the bursa of Fabricius were dispersed with collagenase and trypsin. Light and electron microscopic examination of bursa cell suspensions showed four types of aggregates, identified by low magnification light microscopy as potential nurse cell-like complexes. Electron microscopy revealed that all aggregates consisted of epithelial cells, and complexes of epithelial cells with lymphocytes enclosed were not observed. These findings indicate that interactions similar to those seen in the avian and mammalian thymus between epithelial nurse cells and T lymphocytes are not a part of the avian B cell differentiation process.

Animals↗
PubMed1990

Lymphocyte migration into the skin: the role of lymphocyte homing receptor (CD44) and endothelial cell antigen (HECA-452).

Lymphocyte migration into the lymphoid organs and sites of inflammation is controlled by lymphocyte-endothelial cell interaction at sites where lymphocytes exit from the blood. Expression of Hermes-defined CD44 class of lymphocyte homing receptor and HECA-452 antigen specific for high-endothelium-mediating physiologic lymphocyte extravasation was studied in dermatitis herpetiformis, celiac disease, psoriasis, mycosis fungoides, lymphocytosis cutis, atopic dermatitis, and allergic contact dermatitis. Also, duodenal biopsies of patients suffering from dermatitis herpetiformis or celiac disease were studied for existence of these antigens. Infiltrating lymphocytes in the skin and in the duodenal area expressed homing receptor molecules when studied with monoclonal antibodies, Hermes-1 and Hermes-3, that recognize the CD44 class of molecules involved in lymphocyte binding to high endothelial venules in peripheral lymph nodes, mucosa-associated lymphatic tissues, and inflamed synovium. However, the HECA-452 antigen was not detected on the venules, neither in the skin nor in the duodenum. Even the venules possessing high endothelium morphologically were HECA-452 negative. These findings suggest the CD44 class of lymphocyte homing receptor(s) is also involved in lymphocyte homing to inflamed skin and the duodenal area of the gut. However, on the basis of HECA-452 staining, high endothelial venules in inflamed skin and duodenum are not antigenically identical with high endothelial venules in organized lymphoid tissues. This finding indirectly supports the idea that molecules and/or mechanisms mediating lymphocyte extravasation might be distinct in these organs.

Adult↗
PubMed1989

Lymphocyte homing receptors and adhesion molecules in intravascular malignant lymphomatosis.

Intravascular malignant lymphomatosis (IML) is a highly malignant, recently recognized form of lymphoma. It is characterized by multifocal proliferation of malignant lymphocytes within small blood vessels, primarily in the central nervous system and skin, frequently resulting in circulatory disturbances. The cause of the impaired capability of the malignant lymphocytes to extravasate has remained unclear. We analyzed the presence of immunoreactivity for certain homing receptor and adhesion molecules associated with lymphocyte extravasation in 3 patients with this disease. Compared with non-neoplastic leukocytes, large malignant lymphocytes appeared either negative or only weakly positive for the leukocyte surface glycoprotein, CD18 that is the beta chain of the CDIIa/CD18 complex (lymphocyte-function associated antigen-I, LFA-I), which mediates cell-to-cell adhesion of lymphocytes. On the other hand, antibody to one of the proposed ligands for this complex, intercellular adhesion molecule-I, gave positive reactivity both on lymphocytes and on endothelial cells. Further, the malignant lymphoid cells stained positively with Hermes-3 antibody, which recognizes a common structure of CD44 class of molecules involved in lymphocyte homing. It was also shown that HECA-452 antigen, a marker of high endothelial venules (HEV) supporting lymphocyte extravasation, can be synthesized by an IML patient even at the site of inflammation but it is not prerequisite for extravasation of inflammatory lymphocytes. Our results suggest that the deficiency or absence of the adhesion molecule CDIIa/CD18 may contribute to the inability of the malignant lymphoid cells to extravasate in IML, and perhaps also to the high malignancy of this form of lymphoma.

Aged↗
PubMed1989

Flow cytometric analysis of the Hermes homing-associated antigen on human lymphocyte subsets.

The homing of lymphocytes is controlled by interactions with high endothelial venules (HEV), specialized vessels that define sites of lymphocyte extravasation into lymph nodes and inflamed tissues. In humans, lymphocyte-HEV binding involves a lymphocyte surface glycoprotein (GP) of 85 to 95 kd (CD44, H-CAM), defined by monoclonal antibody (MoAb) Hermes-1. To define the expression of this homing-associated adhesion molecule during human lymphocyte development, we performed two-color immunofluorescence analyses of human bone marrow (BM), thymus, peripheral blood (PB), and tonsillar lymphocytes. The highest levels of Hermes-1 antigen are displayed by circulating B and T cells in the blood, which are uniformly positive and bear roughly twice the level of antigen present on mature lymphocytes within organized lymphoid tissues and BM. "Immature" (CD4+, CD8+) T cells in the thymus are Hermes-1lo to-, whereas thymocytes of mature phenotype (CD4+ or CD8+) are positive. The Hermes-1 antigen is present at high levels on the same population of thymocytes that bears high surface levels of CD3, a component of the T-cell antigen receptor complex, suggesting that levels of T-cell homing and antigen receptors characteristic of mature peripheral T cells appear coordinately during thymocyte maturation/selection. Essentially all T cells in the periphery are Hermes-1hi, including T blasts, and the homing-associated antigen is maintained at high levels on T cells stimulated in vitro by phytohemagglutinin (PHA) and on interleukin-2 (IL-2) maintained T-cell clones and lines. In contrast, although most resting IgD+ B cells are positive a significant fraction of B cells in tonsils are Hermes-1lo to-; these cells are predominantly PNAhi, IgD-, and CD20hi, a phenotype characteristic of sessile, activated B cells in germinal centers. In all lymphocyte populations examined, there is a linear correlation in staining for Hermes-1 and for Hermes-3, an antibody that defines a distinct functionally important epitope on this molecule. The results demonstrate a precise regulation of this homing-associated antigen during lymphocyte differentiation.

Adult↗
PubMed1989

Yersinia antigens in synovial-fluid cells from patients with reactive arthritis.

We examined synovial-fluid cells from 15 patients with reactive arthritis after yersinia infection for the presence of yersinia antigens. Extensive bacterial cultures of the synovial fluid were negative. All the samples were studied by immunofluorescence with use of a rabbit antiserum to Yersinia enterocolitica O:3 and a monoclonal antibody to Y. enterocolitica O:3 lipopolysaccharide. Synovial-fluid cells from 41 patients with other rheumatic diseases served as controls. Synovial-fluid cells from 10 patients with reactive arthritis after yersinia infection stained positively on immunofluorescence; rabbit antiserum and the monoclonal antibody yielded similar results. In most patients the percentage of positive cells ranged from 1 to 10 percent, but in one patient nearly all the cells in the sample stained strongly. Most of the positively stained cells were polymorphonuclear leukocytes, but yersinia antigens were also found in mononuclear phagocytes. All the control samples were negative. Synovial-fluid cell deposits from nine patients were also studied by Western blotting with use of the same antibodies. The results were positive in six of the nine cell deposits from patients with reactive arthritis and in none of the 10 cell deposits from control patients with rheumatoid arthritis. We conclude that in patients with reactive arthritis after yersinia infection, microbial antigens can be found in synovial-fluid cells from the affected joints.

Adult↗
PubMed1989

Human lamina propria lymphocytes bear homing receptors and bind selectively to mucosal lymphoid high endothelium.

It has been hypothesized that the selective recognition of tissue-specific endothelial cell molecules helps determine the in vivo distribution of lymphoid effector cells by controlling the extravasation of their circulating precursors. Here we report (a) immunofluorescence studies of the cell surface phenotype of human lamina propria lymphocytes (LPL), including staining with monoclonal antibody Hermes-1, which defines a 90-kDa lymphocyte surface glycoprotein involved in recognition of high endothelial venules (HEV); and (b) functional analyses of the ability of LPL to bind to HEV in frozen sections of mucosal lymphoid tissues (appendix or Peyer's patch) vs. peripheral lymph nodes. Essentially all LPL bear the Hermes-1 antigen, over 90% at levels comparable to those of circulating PBL. As a population, LPL display a quantitative preference for adherence to mucosal HEV, binding 0.8-1.5 times as well as PBL to mucosal HEV, but only 0.1-0.5 times as well to HEV in peripheral lymph nodes. Of particular interest was the behavior of the lymphoblast fraction, which typically constituted 3-7% of LPL. These cells, defined by size, consisted of a mixture of T cells and surface IgA+ blasts. One hundred percent were Hermes-1 bright, and they bound 4-8 times more efficiently to mucosal HEV than PBL while failing to bind detectably to lymph node HEV. LPL binding to mucosal HEV involves the gp90 Hermes, since the monoclonal anti-gp90 antibody, Hermes-3, and a polyclonal anti-gp90 antiserum inhibit the binding of small LPL and of LP blasts. The remarkable efficiency and specificity of binding by LP blasts may reflect retention of homing properties of the blood-borne precursors of these blasts and is discussed in relation to the capacity of immunoblasts in mesenteric nodes and in thoracic duct lymph to traffic selectively to mucosal lymphoid and extralymphoid sites. The demonstration of organ-specific endothelial cell recognition by LP lymphoblasts provides considerable support for the concept that selective interactions with endothelium play an important role in directing the distribution of activated lymphocyte subsets in vivo.

Antibodies, Monoclonal↗
PubMed1989

The gene for human lymphocyte homing receptor is located on chromosome 11.

The mouse monoclonal antibody Hermes-3 recognizes the human lymphocyte homing receptor. A panel of mouse-human T lymphocyte hybrids, carrying all mouse chromosomes and a limited number of human chromosomes, was analyzed for expression of human homing receptor by indirect immunofluorescence and immunoprecipitation of radiolabeled cell lysates with Hermes-3 antibody. Karyotypic analysis of the tested clones showed that the expression of human homing receptor correlated to the presence of human chromosome 11 in all but one clone. However, concanavalin A induced a weak to moderate expression of the homing receptor in this clone, but not in a chromosome 11- clone. Another clone, heterogeneous for the expression of homing receptor, was separated into a Hermes-3+ and a Hermes-3- fraction with a fluorescence-activated cell sorter. Karyotypic analysis performed after sorting showed human chromosome 11 to segregate with the Hermes-3 antigen. To confirm these data we correlated the expression of two chromosome 11-coded antigens, Trop-4 and Leu-7, with the expression of the homing receptor. In our hybrid clones these three antigens were expressed concordantly. The gene coding for the human lymphocyte homing receptor recognized by Hermes-3 is thus assigned to chromosome 11.

Animals↗
PubMed1988

Biochemical properties of glycoproteins involved in lymphocyte recognition of high endothelial venules in man.

Lymphocyte interactions with high endothelial venules (HEV) are important to the in vivo migration of normal and neoplastic lymphocyte populations. We have previously described an 85- to 95-kDa lymphocyte surface glycoprotein(s) defined by mAb Hermes-1, that is involved in the recognition of HEV by human lymphocytes: antibodies against distinct epitopes of the Hermes-1 Ag differentially inhibit lymphocyte binding to lymph node, mucosal, or synovial HEV. Here we characterize further the Hermes-1-defined glycoproteins. No well defined differences were observed between the Hermes-1 Ag immunoprecipitated from PBL and from mucosa- vs lymph HEV-specific cell lines. The Ag is an acidic (isoelectric point = 4.2) sulfated molecule bearing both O-linked and (3,4) N-linked oligosaccharide side chains. A subset of the Hermes-1-immunoprecipitated species is modified by covalent linkage to chondroitin sulfate, yielding a Mr of approximately 180 to 200 kDa. Pulse-chase labeling reveals a major precursor of 76 kDa that appears to be processed either to the 85- to 95-kDa form or, by addition of chondroitin sulfate, to a 180- to 200-kDa form. The potential role of these structural modifications, and particularly of chondroitin sulfate, in the function of the putative adhesion molecules is discussed.

Animals↗