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G Cox

Publications and source records attributed to G Cox.

At least 19 recordsLinked to original sources
PubMed1994

Manganese superoxide dismutase and heat shock protein 70 are not necessary for suppression of apoptosis in human peripheral blood neutrophils.

We have previously shown that granulocyte (G-CSF) and granulocyte/macrophage (GM-CSF) colony-stimulating factors present in human bronchial epithelial cell conditioned medium (HBEC-CM) suppress apoptosis in neutrophils. In this study, we demonstrate that HBEC-CM also induces increased expression of manganese superoxide dismutase (MnSOD) and heat shock protein 70 (HSP70) in neutrophils. However, treatment of neutrophils with recombinant GM-CSF and G-CSF, which suppressed apoptosis to equivalent degrees, did not induce MnSOD or HSP 70. Thus, we conclude that induction of stress proteins is associated with, but not necessary for, suppression of apoptosis.

Adult↗
PubMed1992

Inhibition of human immunodeficiency virus-1 proliferation by liposome-encapsulated sense DNA to the 5' tat splice acceptor site.

A liposome formulation containing a distearoylphosphatidylethanolamine analog was developed that was endocytosed by both lymphocytes and monocytes. This formulation was used to encapsulate sense and antisense 20-mer oligodeoxynucleotides to the 5' tat splice acceptor site of human immunodeficiency virus type 1. At a DNA concentration of 140 nM, the liposome-encapsulated sense DNA inhibited p24 production by as much as 84% in human peripheral blood leukocytes infected with "wild-type" virus. This treatment also reduced the number of peripheral blood leukocytes producing intracellular viral antigen by 71%. Of interest, no reduction in either parameter was observed for the antisense-containing liposomes. The results demonstrate the promise of a new liposomal delivery vehicle to inhibit human immunodeficiency virus replication by an entrapped oligodeoxynucleotide.

Antiviral Agents↗
PubMed1992

Bronchial epithelial cell-derived cytokines (G-CSF and GM-CSF) promote the survival of peripheral blood neutrophils in vitro.

Neutrophil accumulation in the respiratory tract occurs in a variety of inflammatory disorders, particularly those associated with cigarette smoking. We examined whether bronchial epithelial cells could contribute to this accumulation through the production of factors that increased the survival of neutrophils. Pure primary cultures of human bronchial epithelial cells (HBEC) were used to generate conditioned medium (CM), and the effect of this CM on the survival of neutrophils in vitro was examined. When neutrophils were cultured in control medium, survival was 8.7 +/- 1.7% at 72 h. In contrast, culture of neutrophils in CM resulted in a dose-dependent increase in survival: 22.6 +/- 5.5, 43.6 +/- 4.2, and 64 +/- 3.8% in 1, 10, and 50% CM respectively (mean +/- SEM; P < 0.05). As evidenced by the examination of neutrophil DNA, this prolongation of survival was associated with suppression of apoptosis. Cytokines with known actions on neutrophil biology identified in the CM included granulocyte colony-stimulating factor (G-CSF), granulocyte/macrophage colony-stimulating factor (GM-CSF), and interleukin-8. Through the use of specific neutralizing antibodies, G-CSF and GM-CSF were identified as promoting neutrophil survival. Neutrophil survival was prolonged in the presence of either recombinant human (rh) G-CSF or rhGM-CSF alone in a dose-dependent fashion. In contrast to the response of eosinophils to HBEC-CM, steroid treatment did not prevent the increase in neutrophil survival induced by HBEC-CM. In summary, we show that bronchial epithelial cells markedly increase the survival of human neutrophils in vitro via the release of G-CSF and GM-CSF.(ABSTRACT TRUNCATED AT 250 WORDS)

Apoptosis↗
PubMed1992

Visceral leishmaniasis: a model for infection-induced cachexia.

Parasitic infections and malnutrition coexist in many tropical and subtropical areas. Studies of Leishmania donovani and of experimentally infected Syrian hamsters have provided important insights into the complex interrelationships between malnutrition and this parasitic disease. Malnutrition, which adversely affects cell-mediated immunity, is associated with the development of visceral leishmaniasis (kala-azar) in children living in endemic areas. In turn, L. donovani can cause wasting as well as hepatosplenomegaly, fever, and anemia. Syrian hamsters infected with L. donovani develop a disease that is comparable to that of humans with kala-azar. Weight loss in infected hamsters is associated with splenic macrophage secretion of potentially catabolic cytokines as measured by the D10.G4.1 assay for interleukin-1 and the L929 cytotoxicity assay for tumor necrosis factor/cachectin. Although decreased food intake contributes to wasting in infected hamsters, studies of skeletal muscle function indicate that it is not the sole factor. Leishmania donovani-infected hamsters have also been used to study drugs with the potential to prevent or reverse cachexia.

Adipose Tissue↗
PubMed1992

Synoviocyte derived granulocyte macrophage colony stimulating factor mediates the survival of human lymphocytes.

Synoviocytes have been shown to be effector cells capable of synthesizing and secreting a variety of cytokines and growth factors. We demonstrate here that synoviocyte derived conditioned medium has immunoregulatory properties as it enhances human peripheral blood lymphocyte survival in a dose dependent manner in vitro. The effect elicited by synoviocyte derived conditioned medium from patients with rheumatoid arthritis (RA) was greater than that induced by synoviocyte derived conditioned medium from patients with osteoarthritis. Granulocyte-macrophage colony stimulating factor (GM-CSF) was found in synoviocyte derived conditioned medium with significantly higher levels present in synoviocyte derived conditioned medium from patients with RA. Recombinant human GM-CSF induced survival of human lymphocytes in vitro and a monoclonal antibody to human GM-CSF fully abrogated synoviocyte derived conditioned medium induced survival. Our results demonstrate that synoviocyte derived GM-CSF may be important in the retention of lymphocytes, which is a central pathological characteristic of the rheumatoid joint.

Arthritis, Rheumatoid↗
PubMed1991

Sequence-specific DNA-binding proteins within the Mbcr on the Ph1 chromosome.

The Philadelphia1 (Ph1) chromosome results from a reciprocal translocation between chromosome 9 and chromosome 22, which fuses a portion of the ABL oncogene to the BCR gene, forming the BCR/ABL fusion gene. This produces a fusion protein with a greatly increased protein tyrosine kinase activity in comparison to that of the normal ABL protein. The BCR/ABL gene is transcribed from the promoter of the normal BCR gene, but little is known about the regulation of its expression. In this study, we asked whether there are sequence-specific DNA-binding proteins (DBP) that bind to the breakpoint cluster region (bcr, or Mbcr) within the BCR gene. Sequence-specific DBP located within the Mbcr could have a transcription-regulating effect, and they could participate in the recombination that generates BCR/ABL. Our data show that there are sequence-specific DBP that bind within the Mbcr.

DNA, Neoplasm↗
PubMed1991

Role of herniography in the diagnosis of occult hernias.

Twenty-two patients with groin or incisional pain and normal physical examinations underwent herniography. Eight patients were found to have 11 unsuspected hernias. Seven were direct, two indirect, and two incisional. Six of nine groin hernias were recurrent. Exploration confirmed the herniographic findings in all patients. Follow-up evaluation of patients undergoing herniorrhaphy revealed resolution of symptoms. Ten of the 14 patients with normal herniograms were asymptomatic 3 months after herniography. In these 22 patients, herniography resulted in a savings of $31,000. We conclude that herniography is cost-effective and useful in patients with abdominal wall pain of obscure etiology.

Adolescent↗
PubMed1991

Structural cell-derived cytokines in allergic inflammation.

Based on observations of fluctuations in progenitors for inflammatory cells during allergic responses, we have proposed that a primary determinant of allergic inflammation involves microenvironmental influences on hemopoietic cell differentiation and phenotype; in addition, as a corollary of this, inflammatory cell burden is proposed as an important indicator of the severity and pattern of the inflammatory process in allergy. The studies outlined here focus on the effects of epithelial-cell- and fibroblast-derived cytokines on granulocytic and monocytic cell differentiation and activation in models involving allergic reactions in the upper and lower airways. Pure cultures of nasal or bronchial epithelial cells or fibroblasts are observed to give rise to cytokines important in inducing the differentiation of basophils, eosinophils, neutrophils and monocyte/macrophages. Gene expression, production and secretion of granulocyte/macrophage-colony-stimulating factor, interleukin-6 (IL-6) and IL-8 can be demonstrated in vitro and in vivo. Up-regulation of gene expression and production of these cytokines, which are important in inducing basophil, eosinophil and neutrophil/macrophage differentiation in several assays, is seen with IL-1 and the neuropeptide substance P; conversely, inhibition of cytokine production by structural cells is observed after pretreatment with corticosteroids in vitro, paralleling in vivo effects. Other modulatory effects also examined include: antiallergic compounds, which may affect posttranscriptional events in cytokine production, and heavy metal ions, which can also induce changes in gene expression. Structural-cell-derived extracellular matrices appear also to be important both in mast cell differentiation and in macrophage cytokine gene expression, both of which potentially feedback upon chronic allergic inflammatory processes, leading to their perpetuation.(ABSTRACT TRUNCATED AT 250 WORDS)

Bronchi↗
PubMed1991

Neutrophilic differentiation induced by human upper airway fibroblast-derived granulocyte/macrophage colony-stimulating factor (GM-CSF).

We have established primary lines of fibroblasts from nasal polyp (NP) tissues as well as from normal nasal (NN) mucosa and have examined the ability of these cells to release hormone-like peptide messenger molecules (cytokines). Our results show that human upper airway fibroblasts release granulocyte/macrophage colony-stimulating factor (GM-CSF), granulocyte-CSF (G-CSF), and macrophage-CSF (M-CSF) in vitro. We also show that fibroblasts derived from NP tissue express the gene for GM-CSF at a higher level, and release the GM-CSF product in greater amounts, than NN fibroblasts. In addition, we have examined the ability of these fibroblasts and their conditioned medium (CM) to induce differentiation of human hemopoietic progenitor cells. After 7 d, cultures of these cells in RPMI-10% fetal bovine serum contained 5 +/- 2.5% (mean +/- SD) neutrophils. In contrast, culture of progenitor cells with fibroblasts resulted in significantly greater neutrophilic differentiation (18 +/- 4%). Culture in fibroblast-CM induced a similar degree of differentiation, and fibroblast-CM from NP fibroblasts elicited greater differentiation compared to CM from NN fibroblasts (17.5 +/- 3 versus 12 +/- 3%). The neutrophilic differentiation induced by fibroblast-CM can be fully inhibited by preincubating this CM with a monoclonal neutralizing antibody to human GM-CSF. Thus, our results demonstrate: (1) the ability of human upper airway fibroblasts to release GM-, G-, and M-CSF in vitro; (2) that fibroblasts derived from NP tissues express the gene and release the product GM-CSF at greater levels compared to NN fibroblasts; and (3) that fibroblast-derived GM-CSF causes neutrophilic differentiation of human hemopoietic progenitors.

Animals↗
PubMed1991

Monocyte-macrophage differentiation induced by human upper airway epithelial cells.

We examined the ability of conditioned medium (CM) generated by human upper airway epithelial (Ep) cells from normal (NN) and inflamed, allergic rhinitis (AR) and nasal polyp (NP) tissues to induce monocytic differentiation of hemopoietic progenitors of the HL-60 myeloid leukemia cell line in vitro. In HL-60 cells cultured in RPMI with 10% FBS, there was differentiation to 0.4 +/- 0.4% monocytic cells. NN-, AR-, and NP-EpCM induced differentiation to 23 +/- 6%, 42 +/- 11%, and 71 +/- 10% monocytic cells, respectively. EpCM also induced isolated peripheral blood nonadherent mononuclear cells to express monocyte/macrophage-specific antigens as detected by immunohistochemistry using FMC-32 monoclonal antibodies (anti-CD14). We also examined the cytokine content of these EpCMs and found that they contained granulocyte/macrophage colony-stimulating factor (GM-CSF): 126 +/- 35, 198 +/- 22, and 489 +/- 118 pg/ml for NN-, AR-, and NP-EpCM, respectively. These CMs also contained granulocyte-CSF (G-CSF) and interleukin-6 (IL-6), but there were no significant differences between normal and inflamed tissue-derived cell supernatants. No macrophage-CSF (M-CSF) was detected in these EpCMs. Recombinant human GM-CSF, G-CSF, and IL-6, alone and in combinations, at doses similar to or greater than those found in the EpCMs, did not induce comparable monocytic differentiation of HL-60 cells. Preincubation of the EpCM with neutralizing anti-GM-CSF, anti-G-CSF, or anti-IL-6 antibodies did not significantly inhibit the monocytic differentiation induced by the EpCM.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Differentiation↗
PubMed1991

Promotion of eosinophil survival by human bronchial epithelial cells and its modulation by steroids.

Accumulation of eosinophils in the bronchial tissue occurs in a variety of inflammatory disorders of the human airway. We asked whether airway epithelial cells released factors that could influence eosinophil survival and thus contribute to accumulation of these cells in the tissues. Using conditioned medium (CM) generated from cultured human bronchial epithelial cells (HBEC), we examined the in vitro survival of eosinophils isolated from human peripheral blood. When cultured in control medium, more than 90% of the eosinophils were dead by day 4. In contrast, culture in HBEC-CM resulted in dose-dependent survival at day 6 of 69 +/- 9.4%, 40.5 +/- 5.9%, and 25 +/- 2% viability with 2, 0.5, and 0.1% HBEC-CM, respectively (n = 4). Granulocyte/macrophage colony-stimulating factor (GM-CSF) was detected in the HBEC-CM by enzyme-linked immunosorbent assay at levels of 22 to 48 pg/ml. Furthermore, preincubation of the HBEC-CM with a neutralizing monoclonal antibody to human GM-CSF completely inhibited this increased survival of eosinophils. Because corticosteroids are potent eosinopenic agents, we also examined the effects of the synthetic steroid budesonide on this system. Budesonide inhibited both spontaneous and interleukin-1 (IL-1)-induced GM-CSF production by cultured HBEC. In addition, preincubation of eosinophils with budesonide caused marked abrogation of the survival induced subsequently with either HBEC-CM or recombinant human GM-CSF. In summary, HBEC can support eosinophil survival via the elaboration of GM-CSF and thus may contribute to the local control of inflammatory cell accumulation. Steroids may modulate this process both by inhibiting cytokine production from HBEC and by a direct effect on eosinophils, preventing their response to cytokines.

Antibodies↗
PubMed1991

Choice of anesthetic technique for needle localized breast biopsy.

General anesthesia has been recommended to increase the accuracy and safety of needle localized biopsy (NLB). The authors' NLB experience was reviewed to determine whether the method of anesthesia affected accuracy, yield, complication rate, or cost. All biopsies were performed in a standard operating room using either local anesthesia (Group 1, n = 14), local anesthesia with an anesthesiologist present (Group 2, n = 14), or general anesthesia (Group 3, n = 10). The mean operative times were 54, 59, and 56 minutes for Groups 1, 2, and 3, respectively. In groups 1 and 2, 100 per cent of the specimen radiographs showed the target lesion had been excised, although one biopsy was indeterminate. Among Group 3 two target lesions could not be identified on specimen radiographs and one was indeterminate. There was one malignancy in Group 1 compared with four malignancies in Group 2 and two in Group 3. The average hospital bill was $1,172 for Group 1, $1,418 for Group 2, and $1,488 for Group 3. Anesthesiologists' fees added an additional $224 to Groups 2 and 3. NLB can be performed using local anesthesia without sacrificing accuracy or yield, increasing operative time, or increasing complication rate; the cost is significantly less than with general anesthesia.

Adult↗
PubMed1990

Wasting and macrophage production of tumor necrosis factor/cachectin and interleukin 1 in experimental visceral leishmaniasis.

Wasting and secretion of the catabolic cytokines tumor necrosis factor (TNF)/cachectin and interleukin 1 (IL-1) were assessed in weanling Syrian hamsters infected with Leishmania donovani amastigotes. Whereas the mean weight of uninfected animals increased progressively over 9 weeks, the mean weight of infected animals plateaued at 4-6 weeks and then decreased progressively until death. Splenic mononuclear cells from control hamsters produced 11.3 +/- 8.3 (SD) ng TNF/10(6) mononuclear cells/24 hr. TNF secretion in infected animals was greater than the mean +/- 2 SD of controls in 1 of 3 hamsters at 2 weeks post-infection and in 8 of 9 hamsters at weeks 4-8. The mean TNF secreted by infected animals studied at weeks 4-8 was 371 (range 28-800) ng TNF/10(6) mononuclear cells/24 hr (P = 0.005). Control hamsters produced 7.7 +/- 2.7 pg IL-1/10(6) mononuclear cells/24 hr. At 2 weeks, mononuclear cells from 2 of 3 infected animals secreted amounts of IL-1 greater than the mean +/- 2 SD of controls. All of 8 infected hamsters secreted increased amounts of IL-1 at 4-8 weeks. The mean was 164 (range 17-370) pg IL-1/10(6) mononuclear cells/24 hr (P = 0.002). In comparison to infected animals, mononuclear cells from control hamsters incubated with lipopolysaccharide, 10 micrograms/ml, produced 172.5 ng TNF and 44.6 pg of IL-1/10(6) mononuclear cells/24 hr. The effect of visceral leishmaniasis on food intake was assessed in a separate group of animals housed individually in metabolic cages. Significant reductions in weight and food intake were first observed at 2 and 3 weeks of infection, respectively. By 5 weeks, the food intake of infected animals was 46% that of controls. Syrian hamsters infected with L. donovani provide an excellent model with which to study the mechanism of wasting.

Animals↗