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Biomedical subjects

N K Day

Publications and source records attributed to N K Day.

At least 91 records · Page 5Linked to original sources
PubMed1989

Disulfide-linked gamma delta T cell antigen receptors expressed on T cells derived from patients with primary immunodeficiency disorders.

T cell lines or clones from two patients, one with a partial DiGeorge syndrome and one with severe common variable immunodeficiency expressed disulfide-linked gamma delta T cell antigen receptor (TCR) comprised of a gamma-chain polypeptide of 40-43 kD, and a delta-chain polypeptide of 37-40 kD. This gamma delta TCR appears to be similar to that found on T cell clones, and lines derived from peripheral blood lymphocytes from normal donors. Previous studies have shown that T cell lines derived from the peripheral blood of patients with immunodeficiency disorders express non-disulfide-linked gamma delta TCR. In contrast to the latter and coincident with findings in the present study, the vast majority of T cell lines and clones derived from the peripheral blood of normal donors express disulfide-linked gamma delta TCR.

Antigens, CD↗
PubMed1988

Human IFN-gamma production is inhibited by a synthetic peptide homologous to retroviral envelope protein.

A synthetic 17 amino acid peptide (CKS-17) homologous to a highly conserved region of human and animal retroviral transmembrane proteins was investigated for its influence on the in vitro production of IFN-gamma from human peripheral mononuclear cells. The results showed that CKS-17 coupled to a carrier protein, BSA, inhibited production of IFN-gamma in a dose-dependent manner. Controls, consisting of BSA, which had undergone the coupling procedure or neurotensin coupled to BSA in an identical manner as CKS-17, showed no such inhibition. Reduction in IFN-gamma production could not be attributed to decreased viability of cells, delay of IFN-gamma production or to involvement of suppressor cells. Moreover, inhibition of IFN-gamma production was not related to the inhibition of DNA synthesis. The inhibition appeared to be a direct effect of CKS-17 on IFN-gamma-producing cells. Kinetic studies revealed that this suppression occurred when CKS-17 was introduced to the culture concurrent with or within 48 h after introduction of IFN inducers. Preincubation experiments showed that the presence of CKS-17 in the culture medium was not necessary to exert its inhibitory effect. These results suggest that a portion of retroviral envelope proteins possess important immunomodulatory actions.

Amino Acid Sequence↗
PubMed1988

Guinea pig and gerbil erythrocytes rosette with different cells in the blood, bone marrow, and thymus of the cat.

Cat thymocytes, bone marrow cells, and peripheral blood leukocytes (PBL) formed rosettes with guinea pig (GP) and gerbil (G) erythrocytes (E). In PBL from adult cats the frequency of rosettes was 27% with GPE and GE, while an average of 33% bone marrow cells formed rosettes with GPE and only 4% with GE. Thymocytes from kittens showed a high percentage of rosettes with both GPE and GE (35 to 81%), with the frequency of each type varying with the thymus tested. Fluorescein isothiocyanate labeling of one of the erythrocyte species revealed these cells to be rosetting with different nucleated cells; i.e., a low percentage (3-5%) of the rosettes formed with PBL and bone marrow had both labeled and unlabeled erythrocytes. In contrast, "mixed" rosettes were observed with a significant number of thymocytes, averaging 33% of thymocytes from six animals. A further distinction between the GE- and GPE-rosetting cells was revealed by a monoclonal antibody which blocked GE rosette formation without interfering with the binding of GPE to PBL and thymocytes. PBL could be depleted of either GPE- or GE-rosetting cells, with retention of IgG+ cells and cells capable of rosetting with the second erythrocyte species in the nonrosetting fractions. Stimulation of the latter nonrosetting fractions with pokeweed mitogen for induction of Ig synthesis revealed a T-lymphocyte specificity of the GE- and GPE-rosetting cells. PBL depleted of GE-rosetting cells yielded an increased Ig production, two- to threefold above the control; in contrast, depletion of GPE-rosetting cells from PBL resulted in a failure of the remaining cells to respond. These results suggest that T-suppressor cells of the cat are contained in the GE-rosetting fraction and T-helper cells are rosetted with GPE.

Animals↗
PubMed1988

In vitro production of feline IgG: quantification by an enzyme-linked immunosorbent assay (ELISA).

We report here on the development of a sensitive and convenient enzyme-linked immunosorbent assay (ELISA) for feline IgG by using commercially available reagents and optimizing their concentrations. The reagents employed include goat anti-cat IgG antibody and alkaline phosphatase-conjugated goat anti-cat IgG antibody. The assay described is sensitive, reproducible, and highly specific for feline IgG. The assay was applied for the measurement of feline IgG synthesized and secreted in vitro by peripheral blood mononuclear cells cultured with or without a polyclonal B-cell activator. The amounts of secreted IgG in the supernatants measured by an ELISA correlated well with the numbers of IgG-secreting cells which were induced upon stimulation with pokeweed mitogen and determined by a reverse hemolytic plaque assay.

Animals↗
PubMed1987

Suppressive effect on polyclonal B-cell activation of a synthetic peptide homologous to a transmembrane component of oncogenic retroviruses.

Purified feline leukemia virus, UV light-inactivated feline leukemia virus, and a synthetic peptide (CKS-17) homologous to a well-conserved region of the transmembrane components of several human and animal retroviruses were each studied for their effects on IgG production by feline peripheral blood lymphocytes. Using a reverse hemolytic plaque assay, both the viable virus and the UV-inactivated feline leukemia virus, but not the CKS-17, activated B lymphocytes to secrete IgG. When staphylococcal protein A, a polyclonal B-cell activator, was used to stimulate IgG synthesis by feline lymphocytes, the viable virus, the UV-inactivated virus, and the CKS-17 peptide each strongly suppressed IgG secretion without compromising viability of the lymphocytes. These findings suggest that the immunosuppressive influences of feline leukemia virus on immunoglobulin synthesis may reside in a conserved portion of the envelope glycoprotein that includes the region homologous to CKS-17.

Amino Acid Sequence↗
PubMed1987

Influence of inactivated feline retrovirus on feline alpha interferon and immunoglobulin production.

The effect of ultraviolet-inactivated feline leukaemia virus (UV-FeLV) on the development of feline immunoglobulin-secreting cells (ISC) was investigated using a reverse haemolytic plaque assay. Low concentrations of UV-FeLV at 2 X 10(-4) to 2.0 micrograms/ml stimulated the production of ISC. By contrast, the same concentration of UV-FeLV suppressed the development of pokeweed mitogen (PWM)-driven ISC. Maximum suppression of ISC occurred at 50 micrograms/ml of UV-FeLV. The generation of an interferon resistant to acid, heat and sodium dodecyl sulphate (SDS) in the media of lymphocyte cultures incubated with PWM was also significantly suppressed in the presence of 0.2 microgram/ml of UV-FeLV. These findings suggest that non-infectious viral particles appear to modify feline immunoglobulin and interferon-secreting systems.

Animals↗
PubMed1987

Clearance of retroviremia and regression of malignancy in cats with leukemia-lymphoma during treatment with staphylococcal protein A.

Cats persistently infected with a type C retrovirus (feline leukemia virus; FeLV) were treated either by the extracorporeal perfusion of their plasma through filter columns containing staphylococcal protein A (SPA) or by the intraperitoneal injection of SPA for up to 32 treatments. The clearance of evidence of viral infection occurred during treatment with SPA in 67% of the treated cats with chronic viral infection that had FeLV-related abnormalities other than overt malignancy. This rate of viral clearance is more than 30 times greater than the incidence of spontaneous clearance of persistent FeLV viremia in the untreated cat. Actual clearance of viremia occurred in 28% of all cats treated. Regression of malignancy, which occurred in four of 12 (33%) treated cats, was demonstrated by reductions in tumor size and bone marrow neoplastic cell populations. Immediately preceding or concurrent with these remissions from viral infection and malignant disease, a marked though transient elevation in the plasma level of circulating gamma-like interferon occurred in some responding cats and was followed by the appearance and rising titer of a complement-dependent cytotoxic antibody that reacted with FeLV-infected cells. This IgG antibody was shown by several analyses to be specific for the major viral envelope glycoprotein gp70. Further investigations demonstrated that high levels of FeLV at the cellular level might be responsible for the reduced ability of normal feline lymphocytes to secrete gamma-interferon in response to mitogenic stimuli in vitro. These findings may provide some clue to the variation in the responsiveness of individual cats to immunotherapy with staphylococcal protein A.

Animals↗
PubMed1986

Characterization of a newly established feline lymphoma-derived cell line (BKD) lacking T and B cell surface markers.

A new feline lymphoma-derived cell line, designated BKD, was isolated from an anterior mediastinal tumor. Cells of this line were characterized as lymphoid based on morphology, the lack of intracellular esterase and peroxidase activity, and absence of phagocytic function. In contrast with other established feline lymphoma-derived cell lines, cells of the BKD line lack characteristics of both feline T-cells and B-cells in that they neither form rosettes with guinea pig erythrocytes nor have demonstrable surface or cytoplasmic immunoglobulin. Approximately one third of BKD cells form EAC rosettes, a significant number of rosette forming cells (p = 0.0001) when compared to background sheep E-rosetting activity. In addition, a consistently titratable level of interleukin-2-like activity was produced when BKD cells were coincubated with concanavalin A and phorbol-12-myristate-13-acetate. Chromosome analysis showed that a majority of BKD cells are diploid. This new cell line has been continuously replicating in culture for over one year and produces feline leukemia virus as demonstrated by several analyses.

Animals↗
PubMed1986

Changing manifestations of a chronic feline haematopoietic proliferative disease during immunotherapy with staphylococcal protein A.

A cat with feline leukaemia virus-associated malignant disease was treated by ex vivo immunoadsorption using staphylococcal protein A coated filters. During the 12-week course of treatment, the morphological manifestations of the haematopoietic disease showed a progressive transition from erythroid to myeloerythroid to myeloid predominance, and the disease was preceded by and associated initially and terminally with a blast transformation of lymphoblastic morphology. Necropsy revealed massive meningo-cerebral, as well as hepatic, renal, myeloid, lymphoid, peritoneal and pelvic infiltrations largely consisting of lymphoblastic cells. Evidence of myeloid and erythroid differentiation was present in all the infiltrates. The several possible bases for this shift of morphological expression are considered.

Animals↗
PubMed1986

Partial purification and characterization of feline gamma-like interferon.

Feline interferon (IFN) was produced from spleen cells stimulated by Staphylococcus enterotoxin A (SEA). The IFN was purified by a three-step procedure using controlled pore glass adsorption chromatography, concanavalin A (ConA)-agarose column chromatography and gel filtration. The final product of these procedures which had activity of an IFN appeared as a single peak of activity with molecular weight of approximately 50,000. It was sensitive to acid and heat, suggesting that the isolated material was a gamma IFN. The total recovery of feline gamma IFN was 8.2%. Specific activity was 2.95 X 10(4) unit/micrograms protein and was concentrated 2.8 X 10(4) times. This preparation of purified feline gamma IFN was destroyed completely by 0.1% sodium dodecyl sulfate within 20 min. As an inducer of feline gamma IFN, SEA appeared to produce a more uniform IFN product than did ConA. Further, the presence of 10% ethylene glycol in the sample applied to ConA-agarose column as well as its absence in the elution buffer was effective in reducing contaminating acid- and heat-resistant IFNs in the preparation.

Animals↗
PubMed1986

C1 esterase inhibitor deficiency in X-linked hypogammaglobulinaemia: an anomaly fostering anaphylactoid reactions following intramuscular gammaglobulin administration.

A patient with apparent X-linked agammaglobulinaemia was found to be inordinately susceptible to anaphylactoid reactions to intramuscular injections of gammaglobulin. The patient was found also to have low levels of C1 esterase inhibitor (C1 INH). The possibility that the C1 INH deficiency and in this patient, whether genetic or acquired, fostered the susceptibility to the production of anaphylactoid reactions after gammaglobulin injections urges further studies of the association of C1 INH deficiency and anaphylactoid reactions to gammaglobulin injections. The possibility that C1 INH levels like C1q levels may be low in hypogammaglobulinaemic patients as a consequence of increased catabolism of this regulator of the complement system when IgG levels are low is considered.

Adult↗
PubMed1985

Hypercalcemia in cats with feline-leukemia-virus-associated leukemia-lymphoma.

Three cases of hypercalcemia were recognized among 11 cats presenting with leukemia-lymphoma for ex vivo immunoadsorption therapy using Staphylococcal Protein-A-coated filters. In addition, the initial mean serum calcium concentration of cats with leukemia-lymphoma was significantly higher (P less than 0.005) than that of healthy control cats or feline-leukemia-virus-infected cats without malignancy. During immunotherapy of the hypercalcemic cats, objective reduction in the extent of the malignancies was associated with a small reduction in the serum calcium concentrations. This response to treatment, the lack of skeletal metastasis, and the absence of renal and parathyroid pathologic findings imply that humorally mediated mechanisms may have been responsible for the production of the hypercalcemia.

Animals↗
PubMed1985

Polyclonal induction of immunoglobulin synthesis by feline leukocytes as identified in a reverse hemolytic plaque assay.

Optimal conditions of culture and assay for identification of feline immunoglobulin-secreting mononuclear cells were determined for the staphylococcal protein A-reverse hemolytic plaque assay (SpA-RHPA). Hemolytic plaques were most distinct and numerous when peripheral blood mononuclear cells were stimulated with 6.9 micrograms/ml pokeweed mitogen for 7 days. Immunoglobulin-secreting cells were identified morphologically within a zone of hemolysis utilizing a 1:5 dilution of rabbit anti-cat IgG and a 1:30 dilution of guinea pig complement as developing reagents. The SpA-RHPA system should contribute to an understanding of normal feline T- and B-lymphocyte interactions and will likely aid in the identification and understanding of immune cell dysfunctions associated with chronic feline leukemia virus infection.

Animals↗
PubMed1985

Suppression of gamma interferon production by inactivated feline leukemia virus.

Supernatants from cultures of normal feline lymphocytes stimulated with Staphylococcus enterotoxin A showed antiviral activity, characterized as a gamma-like interferon. With the addition of inactivated feline leukemia virus, markedly less interferon was produced. The reduction in interferon production was not attributable to lowered lymphocyte viability or reduced mitogenic properties of Staphylococcus enterotoxin A and appears to be a direct retroviral effect. This finding may reflect clinically relevant events that may contribute to the development of the feline or human states of acquired immunodeficiency.

Acquired Immunodeficiency Syndrome↗
PubMed1985

Structural and functional similarities between the major hemolymph protein of fall armyworm and cat C4 binding protein of the complement system.

We have investigated the structural and functional similarities between insect (armyworm) major larval serum protein (LSP-I) and mammalian (Cat) C4 binding protein (i) by comparing the major chymotryptic peptide patterns using sodium dodecyl sulfate polyacrylamide gel electrophoresis and (ii) their ability to prevent assembly of classical C3 convertase (EAC142). Both Cat C4 bp and Spodoptera LSP-I are composed of identical subunits of Mr = 75,000 and Mr = 80,000, respectively and generate the characteristic cleavage product of Mr = 50,000 on limited proteolysis. These observations are interpreted as an indication that the major hemolymph protein (LSP-I) of fall armyworm is a homologue of the C4bp of the mammalian complement system.

Amino Acids↗
PubMed1985

Clinicopathologic responses in cats with feline leukemia virus-associated leukemia-lymphoma treated with staphylococcal protein A.

Purified protein A from Staphylococcus aureus Cowan I was injected intraperitoneally or was incorporated in filters ex vivo through which plasma from cats with feline leukemia virus (FeLV)-associated leukemia-lymphoma was passed. Before treatment, 65% of the FeLV-infected cats were anemic, and 70% were thrombocytopenic. Concomitant infections, or immune-mediated disease, was common. During treatment 50% of the cats with FeLV-associated disease improved objectively with normal posttreatment hematocrits, thrombocyte and leukocyte counts, disappearance of dysplastic hematologic elements, and correction of marrow dyscrasias. A 33% response to treatment occurred in cats with unequivocal manifestations of malignant disease and was characterized by reductions in tumor size and marrow and peripheral blood neoplastic cell populations. Clearance of FeLV viremia was documented in 28% of the treated cats. The several possible mechanisms by which treatment with staphylococcal protein A causes reduction in the extent of malignant disease are considered.

Animals↗