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N K Day

Publications and source records attributed to N K Day.

At least 37 records · Page 2Linked to original sources
PubMed1996

Selective gamma-chain T-cell receptor gene rearrangements in a patient with Omenn's syndrome: absence of V-II subgroup (V gamma 9) transcripts.

Only gamma-chain T-cell receptor transcripts utilizing V-1 subgroup gene segments were found in peripheral blood lymphocytes from a patient with Omenn's syndrome. gamma-Chain T-cell receptor transcripts utilizing the V gamma 9 (V-II subgroup) gene segment were absent in peripheral blood lymphocytes from this patient. V gamma 9 J gamma 1.2 C gamma 1 rearrangements are those primarily found in peripheral blood lymphocytes (70 to 85%) from normal donors.

Eosinophilia↗
PubMed1996

Relationship between tumor necrosis factor alpha and feline immunodeficiency virus expressions.

The presence of feline immunodeficiency virus (FIV) proviral DNA, expression of FIV p26 core protein, and production of tumor necrosis factor alpha (TNF-alpha) were assessed in sequential biopsies of spleen and lymph node sections, of mononuclear cells of the peripheral blood, and of the serum of specific-pathogen-free cats during the acute phase of FIV infection. A temporal relationship between TNF-alpha production and FIV p26 expression was noted. Two months following FIV infection, and preceding the detection of FIV viremia, levels of TNF-alpha in serum increased significantly (P = 0.04), and they remained elevated during FIV viremia in the third month postinfection. Immunoprecipitates representing expression of TNF-alpha and of FIV p26 were localized in common foci of lymph nodes of FIV-infected cats during this period of active viremia. With the advent of anti-FIV antibodies, circulating levels of TNF-alpha and p26 antigen and expression of TNF-alpha and p26 in the lymph nodes decreased during the fifth month postinfection, and p26 production became undetectable. With clearance of viremia, burden of proviral DNA in peripheral blood mononuclear cells became reduced (P = 0.041), with provirus remaining integrated principally within lymph nodes (P = 0.046). During aviremia, p26 expression was undetectable in any tissue but remained inducible in vitro. During acute FIV infection, TNF-alpha production and p26 expression are intimately linked.

Animals↗
PubMed1995

Induction of intracellular cAMP by a synthetic retroviral envelope peptide: a possible mechanism of immunopathogenesis in retroviral infections.

A synthetic heptadecapeptide, CKS-17, represents the highly conserved amino acid sequences occurring within the transmembrane envelope protein of many animal and human retroviruses. CKS-17 has been demonstrated to exhibit suppressive properties for numerous immune functions. We have recently shown that CKS-17 acts as an immunomodulatory epitope causing an imbalance of human type 1 and type 2 cytokine production and suppression of cell-mediated immunities. cAMP, an intracellular second messenger, plays an important role in regulation of cytokine biosynthesis--i.e., elevation of intracellular cAMP levels selectively inhibits type 1 cytokine production but has no effect or enhances type 2 cytokine production. Here, we demonstrate that CKS-17 induces dramatic rises in the intracellular cAMP levels of a human monocyte cell line and of human peripheral blood mononuclear cells in a time- and dose-dependent manner. A peptide corresponding to the reverse sequence of CKS-17, used as control, has no effect on intracellular cAMP levels. The cAMP-inducing ability of CKS-17 is significantly blocked by SQ-22536, an inhibitor of adenylate cyclase. These results indicate that CKS-17, a highly conserved component of the transmembrane proteins of immunosuppressive retroviruses, induces increased intracellular levels of cAMP via activation of adenylate cyclase and suggest that this retroviral envelope peptide may differentially modulate type 1 and type 2 cytokine production through elevation of intracellular cAMP levels.

Adenylyl Cyclases↗
PubMed1995

Differential modulation of Th1- and Th2-related cytokine mRNA expression by a synthetic peptide homologous to a conserved domain within retroviral envelope protein.

The influence of a synthetic retroviral peptide, CKS-17, on T helper type 1 (Th1)- or Th2-related cytokines was investigated in human blood mononuclear cells. Cells were stimulated with staphylococcal enterotoxin A, anti-CD3 plus anti-CD28 monoclonal antibodies, or lipopolysaccharide to induce cytokine mRNA. mRNA was detected by a reverse transcription-polymerase chain reaction or Northern blot analysis. CKS-17 down-regulated stimulant-induced mRNA accumulation for interferon gamma (IFN-gamma), interleukin (IL)-2, and p40 heavy and p35 light chains of IL-12, a cytokine that mediates development of Th1 response. CKS-17 up-regulated stimulant-induced mRNA accumulation of IL-10 and did not suppress Th2-related cytokine (IL-4, IL-5, IL-6, or IL-13) mRNA expression. A reverse sequence of CKS-17 peptide, used as a control, showed no such action. Anti-human IL-10 monoclonal antibody blocked ability of CKS-17 to inhibit mRNA accumulation for IFN-gamma but not the CKS-17 suppressive activity of IL-12 p40 heavy chain mRNA. Thus, CKS-17-mediated suppression of IFN-gamma mRNA expression is dependent upon augmentation of IL-10 production by CKS-17. This conserved component of several retroviral envelope proteins, CKS-17, may act as an immunomodulatory epitope responsible for cytokine dysregulation that leads to suppression of cellular immunity.

Amino Acid Sequence↗
PubMed1995

Mammary and submandibular gland epidermal growth factor expression is reduced by calorie restriction.

Calorie restriction reduces mammary mitogenesis and tumorigenesis. To test whether epidermal growth factor (EGF) levels are influenced by calorie intake, 72 four-week-old C3H/HeOu mice were separated into two groups and either fed ad libitum (group AL) or calorie-restricted at a mean 19% (group CR). Three mice from each group were evaluated when 6, 8, 10, and 12 weeks old for submandibular gland transcription of EGF and beta-actin RNA for levels of EGF protein in the submandibular gland, mammary gland, and serum and for immunohistological evidence of EGF protein within the submandibular and mammary glands. Submandibular levels of EGF RNA and protein and mammary and serum levels of EGF protein were similar between dietary groups when mice were 6 and 8 weeks old. Mean EGF:beta-actin RNA transcription in submandibular glands of 12-week-old mice were approximately 10-fold greater in AL compared to CR mice (ratio means, 1.499 versus 0.157, respectively; P < 0.01). Mean submandibular levels of EGF protein were greater in 10-week-old AL compared to CR mice (7017.4 versus 4098.5 ng/mg protein, respectively; P < 0.05) and even greater in 12-week-old AL compared to CR mice (4342.6 versus 137.9 ng/mg protein; P < 0.001). Mean mammary levels of EGF protein were greater among 12-week-old AL compared to CR mice (7.8 versus 5.0 ng/mg protein; P < 0.05). Serum levels of EGF did not differ between dietary cohorts. More anti-EGF immunoprecipitate was present in submandibular and mammary gland sections of 10- and 12-week-old AL compared to CR mice. Lowered EGF levels may contribute to the antiproliferative and antineoplastic effects of calorie restriction.

Animals↗
PubMed1995

Predominance of sterile immunoglobulin transcripts in a female phenotypically resembling Bruton's agammaglobulinemia.

The transcription pattern of the heavy chain immunoglobulin gene locus was analyzed in a 6-month-old female with agammaglobulinemia characterized by the absence of mature B cells in peripheral blood, arrested B cell development in the bone marrow and lack of germinal center development. DNA sequencing provided no evidence of mutations within the coding region of the Bruton's tyrosine kinase gene. Polymerase chain reaction-generated cDNA libraries from blood and bone marrow were screened initially using JH and CH oligodeoxynucleotide probes and VH family-specific probes. Only 10% of the transcripts constituted mature VDJC mu recombinations. Ninety percent of the cDNA were sterile immunoglobulin transcripts comprised of: DJC mu (DH-JHC mu), JC mu (JH-C mu), EC mu (enhancer spliced to C mu), SC mu and IC mu [corresponding to switch (S) and intron (I) regions spliced to C mu]. In the mature immunoglobulin transcripts, VH use indicated germline expression with little evidence of somatic mutation. All cDNA were of the C mu type. Different D segments, D-D joining events and unknown D-like elements were noted in the DJC mu and VDJC mu transcripts. This pattern of immunoglobulin rearrangements, along with the phenotypic cell surface antigen characteristics (CD19-), suggest that an earlier arrest in B cell development than is characteristic of Bruton's X-linked agammaglobulinemia has occurred in this patient.

Agammaglobulinaemia Tyrosine Kinase↗
PubMed1995

Dehydroepiandrosterone inhibits replication of feline immunodeficiency virus in chronically infected cells.

Dehydroepiandrosterone (DHEA) is a steroid hormone produced by the adrenal cortex that serves as an intermediary in sex steroid synthesis. DHEA is produced in abundance by humans and most other warm-blooded animals. Based upon previous reports demonstrating the antiviral and immunostimulatory activities of DHEA and DHEA-sulfate (DHEAS) we sought to determine whether introduction of these compounds would affect replication of feline immunodeficiency virus (FIV) in chronically infected cells. When cell number, cell viability, cellular DNA synthesis, and levels of FIV reverse-transcriptase (RT) were measured in cell cultures treated with various dilutions of DHEA or DHEAS it was found that the production of FIV RT was inhibited by DHEA at levels where cellular viability and DNA synthesis were not affected. At the concentrations tested DHEAS did not inhibit FIV replication or impact on cellular viability or proliferation.

Animals↗
PubMed1995

Immunosuppressive retroviral peptides: cAMP and cytokine patterns.

The mechanism(s) by which retroviral proteins exert immunosuppressive influences has remained enigmatic. Here, Soichi Haraguchi, Robert Good and Noorbibi Day propose that induction of intracellular cAMP by a synthetic, immunosuppressive, retroviral envelope peptide causes a shift in the cytokine balance, leading to suppression of cell-mediated immunity by upregulation of interleukin 10 (IL-10) and downregulation of IL-2, IL-12 and tumor necrosis factor alpha production. This may be a crucial step towards generation of immune dysfunction.

Amino Acid Sequence↗
PubMed1995

Shwachman-Diamond syndrome associated with hypogammaglobulinemia and growth hormone deficiency.

Shwachman-Diamond syndrome is a rare congenital disorder of unknown etiology. Characteristic abnormalities of this disease include pancreatic insufficiency, skeletal anomalies, growth retardation, recurrent infections, and hematologic abnormalities. Significant morbidity and mortality in these patients result from respiratory infections, which are not well explained on the basis of neutrophil defects. We have had the opportunity to perform an in-depth clinical immunologic and endocrinologic evaluation of a patient with this syndrome with recurrent respiratory tract infections. She was found to have profound humoral immunologic defects, and serum thymulin was absent. In addition, endocrinologic evaluation for growth retardation revealed growth hormone deficiency. The patient responded to treatment with supplemental growth hormone and intravenous gammaglobulin with accelerated growth and cessation of infections. This case is unique in that it links growth hormone deficiency and hypogammaglobulinemia in a non-X-linked manner and may provide the basis for treatment of other patients with this rare syndrome.

Agammaglobulinemia↗
PubMed1995

Immunomodulation by cells of mononuclear phagocyte lineage in acute cold-stressed or cold-acclimatized mice.

Immunoregulatory states in acute cold-stressed or cold-acclimatized mice were investigated. When male C57BL/6 mice were exposed to environmental temperature of 5 degrees for 24 hr (acute cold stress), the spleen cells showed depressed proliferative responses to stimulation with concanavalin A (Con A) or lipopolysaccharide (LPS) compared with control mice (reared at 25 degrees). The proportion of Thy-1.2+ cells increased significantly in spleens from these acute cold-stressed mice. The Con A responses of T-enriched cells from acute cold-stressed mice were restored to the normal level by adding plastic-adherent cells from control mice. Further, adherent cells from acute cold-stressed mice markedly suppressed the Con A responses of control spleen cells. Thus, the plastic-adherent cells appeared to be responsible for the suppressed Con A responses. On the other hand, proliferative responses to Con A or LPS were elevated in spleen cells from mice exposed to 5 degrees for 3 weeks (cold acclimatization). A significant decrease of Thy-1.2+ cells was detected in these spleens. It was shown that the enhanced proliferative responses were attributable to functional alterations of the plastic adherent cell population but not to those of lymphoid cell population. These findings indicate that the low or high responsiveness of spleen cells to Con A observed in cold-stressed or cold-acclimatized mice, respectively, may be due to a mechanism including the contrary modulations of functions of cells of mononuclear phagocyte lineage.

Adaptation, Physiological↗
PubMed1994

Calorie intake during mammary development influences cancer risk: lasting inhibition of C3H/HeOu mammary tumorigenesis by peripubertal calorie restriction.

To test for a relationship between peripubertal calorie intake, mammary development, and tumorigenesis, weanling C3H/HeOu mice were separated into 3 groups: fed diet either ad libitum (AL) and designated group AL (n = 60); fed a similar, calorie-restricted (CR) diet only during mammary development when 4-12 weeks old and then subsequently fed ad libitum when > or = 13 weeks old (group CR4-12, n = 24); or continuously calorie restricted (group CR, n = 60). Eight weeks of peripubertal calorie restriction provided CR4-12 mice with lasting protection from mammary tumorigenesis (P = 0.004) and lowered cumulative tumor incidence by 33% compared to AL mice. Sustained calorie restriction of group CR mice further reduced mammary tumor incidence compared to both AL (P = 0.000001) and CR4-12 mice (P = 0.009). Calorie intake significantly influenced mammary development and cellular proliferation. Compared to the mammary development of AL mice, calorie restriction reduced the diameter of ductal end buds (189 microns compared to 146 microns; P < 0.01), lowered the end bud [3H]thymidine labeling index from > or = 20 to < or = 13% (P < 0.001), delayed end bud migration and mammary glandular growth (P < 0.01), reduced alveolar budding (P < 0.001), reduced the proportion of alveoli containing at least one [3H]thymidine labeled cell from > or = 50 to < or = 22% (P < 0.001), and lowered the alveolar [3H]thymidine labeling index of labeled alveoli from > or = 14 to < or = 7% (P < 0.001). These findings link peripubertal calorie intake, mammary development, and carcinogenic risk, and show that the abrogation of mammary tumorigenesis by calorie restriction is partially attributable to influences on mammary development.

Animals↗
PubMed1994

A method of purifying feline T lymphocytes from peripheral blood using the plant lectin from Pisum sativum.

The binding properties of several plant lectins on feline peripheral blood lymphocytes (PBL) were examined by flow cytometry to reveal if any could serve as probes for identifying specific lymphocyte subclasses. Most of the lectins bound > or = 90% of PBL in a uniform manner. The exceptions were the lectins from Glycine max, Phaseolus limensis, and Dolichos biflorus, which bound only a proportion of the PBL. The differential binding of the lectins to lymphocyte subclasses was examined by comparing the staining of control PBL to T cell-depleted PBL. The lectins from Pisum sativum, Lens culinaris, succinylated Triticum vulgaris, and Dolichos biflorus stained T-depleted PBL more brightly than control PBL. Extensive cytofluorometric analyses of the binding properties of Pisum sativum agglutinin (PSA) on feline PBL and mesenteric lymph node cells indicated that feline B lymphocytes express more higher affinity surface receptors for PSA than do T lymphocytes. The higher affinity binding of PSA to B lymphocytes was further demonstrated by PSA-mediated cellular affinity chromatography. With this procedure it was possible to deplete PBL of B lymphocytes and to obtain pure populations of feline T lymphocytes.

Animals↗
PubMed1994

Detection of cell specific cluster determinant expression by reverse transcriptase polymerase chain reaction.

We describe a new, rapid, sensitive, and reproducible method for examining gene expression of several cell specific surface cluster determinants, CD2, CD3-gamma, CD4, CD8-beta, CD14, CD19, CD20, CD23, and CD25-alpha, and terminal deoxynucleotidyl transferase which heretofore have been commonly detected by flow cytometry. The method presented uses the reverse transcriptase polymerase chain reaction (RT-PCR) to analyze CD gene expression in stable human cell lines, peripheral blood lymphocytes, bone marrow, and lymph node cells. Polymerase chain reaction products were quantitated by incorporation of radiolabeled nucleotide during PCR and the amount of nucleotide incorporated into DNA was measured by ion exchange filter chromatography. The usefulness of this methodology is demonstrated in an analysis of peripheral blood samples from a patient who presented with B cell deficiency. Results of analyses of peripheral blood samples from this patient by flow cytometry and RT-PCR are similar except that the increased sensitivity of RT-PCR permitted the detection of CD19, CD20, and CD23 in the blood samples of this patient who otherwise appeared to be lacking in all markers of B cell development.

Antigens, CD↗
PubMed1994

Bone marrow transplantation therapy using resistant donors for retrovirus-induced leukaemia in mice.

Infection with Rauscher leukaemia virus (RLV) causes erythroleukaemia, anaemia, viraemia, and splenomegaly, features which develop very quickly in mice of strains susceptible to RLV but more slowly or not at all in strains resistant to RLV. We compared the effects of bone marrow transplantation (BMT) of donor cells obtained from a mouse strain resistant to the virus with the effects of BMT of donor cells obtained from strains susceptible to the virus, in recipient virus-susceptible mice which had previously been inoculated with RLV. Our results indicated that bone marrow transplantation from a marrow-resistant donor, but not from a susceptible donor, delayed the expression of leukaemia and delayed death, although such treatment did not appear to inhibit viral infection in susceptible recipients.

Acquired Immunodeficiency Syndrome↗
PubMed1994

Alteration of in vivo cytokine gene expression in mice infected with a molecular clone of the defective MAIDS virus.

The discovery of T helper type 1 (Th1) and T helper type 2 (Th2) phenotypes within the CD4+ T-lymphocyte population has allowed for further elucidation of the roles the T cells play in regulation of humoral and cellular immunity. It is suggested that differential activation of the CD4+ subsets, particularly up-regulation of the Th2 cell and down-regulation of the Th1 cell, may be associated with diseases as diverse as AIDS and asthma. We report herein that by using the polymerase chain reaction to analyze the kinetics of in vivo cytokine- and virus-specific gene expression, we can show that mice infected with the molecularly cloned MAIDS defective virus 1/27/A BM5 exhibit an alteration in cytokine gene expression that closely parallels an increase in spleen cell numbers, an increase in IgM production, a decrease in the stimulation index, and an increase in defective-virus gene expression in these mice. As has been suggested to be true for human AIDS, the observed alteration of cytokine gene expression suggests that a pattern of expression similar to that produced by Th2 cells may also have a role in the development of MAIDS.

Animals↗