Biomedical subjects

D Armellino

Publications and source records attributed to D Armellino.

4 recordsLinked to original sources

PubMed1991

Clinical significance of neutropenia in patients with human immunodeficiency virus infection.

OBJECTIVE: To determine the incidence of infection in human immunodeficiency virus (HIV)-infected patients during periods of neutropenia and non-neutropenia. To compare the infection rates in patients with HIV disease to those in a group hospitalized with neutropenia and hematologic malignancy. DESIGN: Prospective observational study conducted between December 1985 and December 1987 at a university teaching hospital. Thirty patients with documented acquired immunodeficiency syndrome (AIDS) and absolute T-helper cells less than 200 mm/mm3. All patients had a period of non-neutropenia following a neutropenic period (neutrophils less than 1000 cells/mm3). RESULTS: The rate of first infection during neutropenic and non-neutropenic periods for opportunistic infection and nonopportunistic infections were compared. There were no differences between infection rates for the two time periods for both types of infections. A subgroup of patient care days in which non-neutropenic days followed neutropenic days also was studied to eliminate selection bias. In this group, a comparison of infection rates also revealed no difference between neutropenic and non-neutropenic periods. An alternate analysis of the time until first infection during periods of neutropenia or non-neutropenia was done using the Kaplan-Meier product limit method. There was a longer infection-free period for the neutropenic group for opportunistic infections, but it was not statistically significant (p less than .1). In addition, we compared HIV-infected patients with a group of 37 patients with neutropenia from hematologic malignancy. There was a significantly higher rate of all infections, particularly bacteremias (p less than .001), in the group of patients with hematologic malignancies when compared with all subsets of patients with HIV disease. CONCLUSION: We conclude that patients with HIV disease and modest neutropenia do not have an increased risk of bacterial infection. The incidence of all infections is significantly greater in patients with neutropenia secondary to hematologic malignancy.

Acquired Immunodeficiency Syndrome↗

PubMed1991

Structure/activity relationships in basic FGF.

Although the FGFs have been subject to extensive biological studies, only limited progress has been made so far in determining the critical elements of structure-activity relationships in the FGFs. Among the recognized structural elements with potential to affect the biological activity of FGFs are the cysteine residues, and the heparin- and receptor-binding domains. These features have been studied using a variety of experimental approaches, but the available data are inconclusive. For example, ambiguity regarding the presence of a disulfide structure in FGFs was not resolved until the availability of x-ray crystal structure data. Furthermore, the functionally important heparin- and receptor-binding domains have been poorly characterized, with some interpretations being controversial. In this report, we describe a novel fragment of basic FGF (bFGF) with high biological activity [Ser78,96-bFGF(70-153)]. This fragment was generated by pronase treatment of heparin-bound recombinant Glu3,5Ser78,96-bFGF mutant and is active in vitro at an ED50 of about 100 ng/ml. The structure of the fragment and the manner by which it was generated provide additional insight into important aspects of structure-activity relationships in FGFs. Specifically, we conclude that (a) the cysteines in our bFGF mutant do not form a disulfide bond, (b) the high-affinity heparin binding of bFGF critically depends on an intact 3-dimensional structure of the growth factor rather than on specific heparin-binding sequence domains, and (c) the bFGF sequence between residues 70 and 122 is important for high biological activity.

Binding Sites↗

PubMed1989

IFN-gamma and IFN-alpha induce the expression and synthesis of Leu 13 antigen by cultured human endothelial cells.

Leu 13 is a 16 kDa human lymphocyte surface Ag and monoclonal anti-Leu 13 induces T cell aggregation and alters T cell proliferation. In previous studies using anti-Leu 13, Leu 13 Ag has been detected on endothelial cells (EC) of arteries, capillaries, and veins in human tissue sections. In contrast, in this study using the same antibody, Leu 13 Ag could not be detected on unstimulated cultured human umbilical vein endothelial cells (HUVEC) by indirect immunofluorescence, immunoperoxidase staining, or immunoisolation of radiolabeled Ag from labeled endothelial cells. However, when HUVEC were cultured with IFN-gamma, Leu 13 Ag was demonstrable using all three detection techniques. Leu 13 Ag was detectable after 24 h of incubation with IFN-gamma (30 U/ml) and was maximally expressed after 72 h. After removal of IFN-gamma, Leu 13 Ag progressively declined back to basal levels by 4 days. Induction of Leu 13 Ag expression by IFN-gamma was suppressed by cycloheximide. Although Leu 13 Ag expression was also induced by IFN-alpha, PMA, and IL-1 were inactive. When HUVEC were incubated with IFN-gamma, surface-labeled with 125I, and then solubilized, anti-Leu 13 immunoisolated a 16-kDa radioactive band that comigrated with Leu 13 immunoisolated from T cells. Similar results were obtained using HUVEC that were metabolically labeled with 35S-methionine. These results demonstrate that HUVEC stimulated with IFN-gamma and IFN-alpha express Leu 13 Ag on their surface and suggest that exposure of EC to IFN may induce EC to develop new functional properties at sites of inflammatory and immune reactions.

Antibodies, Monoclonal↗

PubMed1985

Biosynthesis of functionally active heparin cofactor II by a human hepatoma-derived cell line.

Human plasma heparin cofactor II (HCII) inhibits thrombin by rapidly forming a stable, equimolar complex in the presence of heparin or dermatan sulfate. Cultured human hepatoma-derived cells (PLC/PRF-5) secreted (approximately equal to 200 ng/ml in 3 days) a protein of MW - 72 kD that was immunoisolated and immunoblotted with anti-HCII, co-migrated on SDS-PAGE with human plasma HCII, and formed covalent complexes with thrombin (MW - 101 kD) in the presence but not absence of heparin or dermatan sulfate; these complexes co-migrated with those obtained by incubating thrombin with human plasma under the same conditions. HCII was not detectable (less than 0.13 ng/ml) in post-culture medium from cultured human umbilical vein endothelial cells or human foreskin fibroblasts.

Antibody Specificity↗