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Biomedical subjects

A H Cross

Publications and source records attributed to A H Cross.

62 records · Page 4Linked to original sources
PubMed1990

Homing to central nervous system vasculature by antigen-specific lymphocytes. II. Lymphocyte/endothelial cell adhesion during the initial stages of autoimmune demyelination.

A previous study from this laboratory on adoptively transferred experimental allergic encephalomyelitis (EAE) induced by myelin basic protein-responsive (MBP+) 11C-labeled lymphocytes showed that MBP+ cells entered the central nervous system (CNS) before signs, migrated through the endothelium, and remained within the perivascular space. The majority of cells effecting CNS damage were nonradiolabeled and appeared to be host-derived and non-CNS antigen specific. The present study defined the immunocytochemical and initial structural events occurring between lymphocytes and endothelial cells (EC) on CNS blood vessels during EAE induced with MBP+ lymph node cells or T-cell lines. Monoclonal antibodies against lymphocyte function-associated molecule LFA-1 and its ligand, intercellular adhesion molecule-1 (ICAM-1), and the addressin MECA-325, a marker of mouse lymph node high endothelial venules, were tested on frozen sections in combination with the avidin-biotin-complex technique. The attachment and infiltration of lymphocytes correlated with the onset of signs and the appearance in the CNS of MECA-325 and ICAM-1 on vessels with cellular infiltrates and sometimes with plump EC. The cellular infiltrates were composed largely of LFA-1+ lymphocytes. Ultrastructurally, pseudopodia from lymphocytes were seen to attach to and penetrate EC in the CNS and form small gap junction-like contacts. On the EC surface, some processes from lymphocytes made larger synapse-like contacts while others were associated with coated pits suggestive of receptor mediation. The results are in accord with specific homing and attachment of lymphocytes to the CNS vasculature being early features of the disease process in EAE and with some CNS vessels acquiring properties of lymph node elements. Understanding of the mechanisms underlying these lymphocyte/EC interactions has therapeutic import for multiple sclerosis, for which EAE is the prime model.

Animals↗
PubMed1989

Axonal dystrophy as a consequence of long-term demyelination.

Central nervous system lesions in guinea pigs sensitized for chronic relapsing experimental allergic encephalomyelitis for between 18 and 36 months have been found to possess a small but probably significant degree of axonal involvement. Axonal identity was established by light and electron microscopy and immunocytochemistry. The axonal changes were restricted to white matter and consisted of massive (up to 95 microns) scattered axonal spheroids which displayed lateral branches and vacuoles; small groups of spheroids filled with a wide assortment of axoplasmic organelles; and deeper, more extensive collections of affected demyelinated axons and spheroids which frequently displayed abortive axonal regeneration into the Virchow-Robin space. Although accumulations of most axoplasmic organelles occurred in the spheroids and reactive axons, microtubules were relatively rare. These formations were never seen in adjacent unaffected white matter and spinal cord tissue from normal aged animals contained only the occasional spheroid. It is hypothesized that the disease process in experimental allergic encephalomyelitis may be more dynamic than previously described and that prolonged interruption in normal axon-glial relationships in chronically demyelinated (sometimes remyelinated) gliotic lesions might lead to a block in axoplasmic transport and a disruption of the axonal cytoskeleton. Although most affected axons appeared intact, some of the spheroids probably represented proximal stumps from which sprouting occurred, leading to neuroma-like formations. The implications of the findings are discussed in reference to long-term demyelination and multiple sclerosis where almost identical profiles have been documented.

Animals↗
PubMed1988

Acute myeloid leukemia with T-lymphoid features: a distinct biologic and clinical entity.

We studied the clinical and biologic features of 10 cases of acute leukemia that met standard French-American-British (FAB) criteria for acute myeloid leukemia (AML) but in which the blast cells also expressed the T-cell-associated CD2 surface antigen. All cases had greater than 3% myeloperoxidase and Sudan black B-positive leukemic blasts, and blasts from seven cases contained Auer rods. Reactivity of the cells with a panel of monoclonal antibodies (MAbs) indicated that leukemic cells in all cases expressed myeloid-associated (CD11b, CD13) surface antigens, further supporting the diagnosis of AML. However, blasts from every patient coexpressed the T-cell-associated surface CD2 and CD7 as well as cytoplasmic CD3 antigens. Blasts from five patients expressed surface CD25, whereas blasts from only one expressed surface CD3. Five patients had rearranged T-cell receptor beta-chain genes, whereas only three had rearranged T-cell receptor gamma-chain genes. This pattern of lineage-related gene expression appears to define a distinct subtype of AML with T-lymphoid features (CD2+ AML) and could reflect either aberrant gene expression in leukemic blasts or transformation of a pluripotent stem cell having a flexible pattern of gene expression. Clinically, these 10 patients presented at an older age with a higher leukocyte count and a higher frequency of lymphadenopathy than did children whose blast cells were characteristic of myeloid leukemia. Patients with CD2+ AML also had poorer responses to remission induction therapy (50% v 80% entered complete remission, P = .05). However, each of the five children who failed induction chemotherapy on AML protocols had a striking response to drug combinations usually reserved for lymphoid leukemia. We conclude that this leukemia with mixed lymphoid and myeloid characteristics is a distinct biologic and clinical entity.

Adolescent↗
PubMed1987

Provocative pattern of rearrangements of the genes for the gamma and beta chains of the T-cell receptor in human leukemias.

To examine the distribution of rearrangements of the gamma- and beta-chain T-cell receptor (TCR) genes in T- and non-T acute lymphoblastic leukemias (ALLs), and potentially to determine which genes rearrange first in ontogeny, we analyzed high molecular weight DNA from 102 patients with acute leukemia. Rearranged gamma- and beta-chain genes were found in all T-cell ALLs (22/22) examined. Overall, 27% (18/66) of B-lineage ALLs had beta-chain gene rearrangements, and 41% (24/58) had gamma-chain gene rearrangements, but the distribution of rearranged genes varied according to the stage of B-cell differentiation. The gamma-chain genes were rearranged in 11% (1/9) of the B-lineage patients negative for the common acute lymphoblastic leukemia antigen (cALLA) and 50% (23/46) of cALLA+ ALL patients, while the beta-chain genes were not rearranged in any of the 7 cALLA- ALL patients examined but were rearranged in 32% (18/56) of the cALLA+ patients. Neither TCR gene was found to be rearranged in acute nonlymphoid leukemia patients (0/12) or in patients with B-cell (surface immunoglobulin-positive) leukemia (0/3). Of the 44 cALLA+ patients in which a direct comparison of gamma- and beta-chain gene rearrangements could be made, 34% had both genes rearranged, 16% had only gamma-chain gene rearrangements, and the remaining 50% had both genes in the germ-line configuration. beta-Chain rearrangements have not been found in the absence of gamma-chain rearrangements, thus supporting a proposed hierarchy of TCR gene rearrangements. A provocative finding was that only a small percentage (11%) of the patients with cALLA- B precursor cell ALLs had rearranged TCR genes, while 50% of the cALLA+ leukemia patients had at least gamma-chain rearrangement, raising a question as to whether indeed cALLA- cells are precursors to cALLA+ cells. Interestingly, 18% (2/11) of the cytoplasmic immunoglobulin (cIg)-positive cALLA+ (pre-B) ALLs involved TCR gene rearrangements, compared to 60% (21/35) of the cIg-negative cases, suggesting the possibility that the majority of functional B cells are derived from the cALLA+ pool that contains immunoglobulin but not TCR gene rearrangements.

Adolescent↗
PubMed1987

Adoptively transferred acute and chronic relapsing autoimmune encephalomyelitis in the PL/J mouse and observations on altered pathology by intercurrent virus infection.

PL/J mice developed chronic relapsing experimental allergic encephalomyelitis (EAE) after receiving syngeneic guinea pig basic protein (GPBP)-immune lymph node cells or spleen cells which were cultured in the presence of GPBP or the encephalitogenic N-terminal peptide of GPBP. The presence of L3T4+ cells and in vitro proliferation in response to GPBP are required for the successful transfer. Pathologically, passively transferred EAE in the virus-free PL/J strain was characterized by an infiltration in the central nervous system by small lymphocytes, followed by the appearance of macrophages, and subsequently by primary demyelination. These findings were similar to those previously observed in chronic relapsing EAE in SJL/J mice. However, in some experiments pathologic examination of the spinal cord showed large demyelinating lesions which were necrotic and infiltrated with eosinophilic polymorphonuclear leukocytes. Sera from mice with this pathology contained antibodies to murine hepatitis virus and extensive search identified a few areas of coronavirus replication. The pathology of autoimmune mediated demyelination may be altered in the presence of coronavirus infection but the clinical pattern of EAE expression did not differ between virus-free and coronavirus-infected mice.

Animals↗
PubMed1986

Mediating influences of social support: personal, family, and child outcomes.

The mediating influences of social support were examined in a study of 137 parents of mentally retarded, physically impaired, and developmentally at-risk children. Social system theory was used as a conceptual framework for assessing the effects of social support on personal well-being, parental attitudes toward their child, family integrity, parental perceptions of child functioning, parent-child play opportunities, and child behavior and development. A series of hierarchical multiple regression analyses by sets, controlling for family SES and income, child sex and age, and child developmental quotient and diagnosis showed that both satisfaction with support and number of sources of support had main and/or interactive effects in all sets of outcome measures. More supportive social networks were associated with better personal well-being, more positive attitudes, and more positive influences on parent-child play opportunities and child behavior and development. Findings were discussed in terms of both methodological and conceptual contributions to understanding the broad-based influences of social support.

Attitude↗