Search PubMed⌕ Search

Biomedical subjects

G Cox

Publications and source records attributed to G Cox.

At least 109 records · Page 6Linked to original sources
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↗
PubMed1989

Gastric mucosal nodules due to cytomegalovirus infection.

We report a patient who developed cytomegalovirus infection after receiving a heart transplant. Nodular gastric lesions were noted on radiologic and endoscopic examinations. Endoscopic biopsy provided early evidence of cytomegalovirus infection.

Aged↗
PubMed1989

Demographic and clinical features predictive of recovery in acute mania.

Discrepancies exist in previous reports regarding clinical and demographic features associated with recovery in acute mania. The authors studied 44 hospitalized patients with bipolar affective disorder, manic type. They report a significant association between more depressive symptomatology and perhaps younger age of illness onset, and poor immediate treatment response. They also found the total amount of psychopathology at admission, as measured by the Brief Psychiatric Rating Scale and Manic State Rating Scale, and the degree of psychosis to be unrelated to immediate outcome. The authors suggest that the not recovered manic subgroup has a distinct illness or a variant of bipolar disorder with poor prognosis that warrants further and separate investigation.

Acute Disease↗
PubMed1989

Human lung fibroblast-derived granulocyte-macrophage colony stimulating factor (GM-CSF) mediates eosinophil survival in vitro.

Tissue eosinophilia has been reported to occur in pulmonary fibrosis, a disease characterized by chronic inflammation and lung fibroblast proliferation. We have examined the in vitro interaction of these two cell types by determining the in vitro survival of human peripheral blood eosinophils co-cultured with human lung fibroblasts. Survival of eosinophils cultured alone was 10% at day 3 and less than 1% at day 7. In contrast, survival of eosinophils that had been co-cultured with fibroblasts was 98, 90, 73, and 69% at days 3, 7, 10, and 14, respectively. Fibroblast-conditioned medium (CM) elicited a similar result in a dose-dependent fashion. Survival of eosinophils cultured with CM which had been preincubated with a monoclonal-neutralizing antibody to human GM-CSF was inhibited in a dose-dependent manner. Human recombinant-derived GM-CSF supported eosinophil survival in the dose-dependent fashion. Survival at day 7 of eosinophils treated with one single dose of GM-CSF (10 U/ml) was 64%. The effect of fibroblast-CM on eosinophils likely represents true survival since eosinophil proliferation as determined by [3H]thymidine incorporation did not occur. We also report that freshly isolated eosinophils had normal ultrastructural, scanning and transmission electron microscopy characteristics, and were normodense. In contrast, eosinophils co-cultured for 7 days with fibroblasts acquired irregular shapes and became hypodense and partially degranulated. Thus, our results indicate that human lung fibroblast-derived GM-CSF mediates the in vitro survival of human eosinophils.(ABSTRACT TRUNCATED AT 250 WORDS)

Antibodies↗
PubMed1988

The proton pore in the Escherichia coli F0F1-ATPase: substitution of glutamate by glutamine at position 219 of the alpha-subunit prevents F0-mediated proton permeability.

Three mutations in the uncB gene encoding the a-subunit of the F0 portion of the F0F1-ATPase of Escherichia coli were produced by site-directed mutagenesis. These mutations directed the substitution of Glu-219 by Gln, or of Lys-203 by Ile, or of Glu-196 by Ala. Strains carrying either the Lys-203 or Glu-196 substitutions showed growth characteristics indistinguishable from the coupled control strain. Properties of membrane preparations from these strains were also similar to those from the coupled control strain. The substitution of Glu-219 by Gln resulted in a strain which was unable to utilise succinate as sole carbon source and had a growth-yield characteristic of an uncoupled strain. Membrane preparations of the Glu-219 mutant were proton impermeable and the F1-ATPase activity was inhibited by about 50% when membrane-bound. The results are discussed with reference to a previously proposed intramembranous proton pore involving subunits a and c.

Escherichia coli↗
PubMed1988

Phase II trial of idarubicin in patients with advanced lymphoma.

A phase II trial of idarubicin was performed in 24 patients with advanced lymphoma. The drug was administered in a dose of 10-15 mg/m2 i.v. or 15-70 mg/m2 p.o. (single dose) every 3 weeks. There were four partial responses and four minor responses. All but one of the responders had received prior doxorubicin therapy. The toxicities were myelosuppression, nausea and vomiting, and alopecia. Two patients with compromised cardiac function were observed to have further deterioration in the ejection fraction as measured by gated cardiac scan after idarubicin therapy. Further assessment of the activity of idarubicin against lymphoma is recommended in less heavily pretreated patients. The cardiac toxicity should be carefully monitored in future studies.

Antibiotics, Antineoplastic↗
PubMed1986

Acquired perforating disease in oil field workers.

Eight cases of an acquired perforating disease are reported in oil field workers who were exposed to drilling fluid. Analysis of the drilling fluid showed it to contain many components, including calcium chloride. Histopathologic study of patient lesions demonstrated transepidermal elimination of calcium. An in vivo mouse model was developed to study this phenomenon, which may represent a calcium-mediated perforating disorder.

Adult↗
PubMed1982

A therapeutic comparison of ipratropium bromide and salbutamol in asthmatic patients.

A single-blind, crossover study was carried out in 43 asthmatic patients to compare the efficacy and tolerance of inhaled ipratropium bromide with inhaled salbutamol. One or other drug was given 3-times daily (0.04 mg ipratropium bromide or 0.2 mg salbutamol per dose) over a period of 4 weeks. Patients were then crossed over to the alternative medication for a further 4 weeks. The results of lung function tests performed at routine clinic visits and by the patients at home showed similar increases in peak flow and spirometry recordings, although more patients expressed a preference for salbutamol. Unwanted effects were minor with both drugs. It is suggested, therefore, that ipratropium bromide may be a useful alternative to beta-stimulants in some asthmatics.

Adult↗
PubMed1981

Actin acetylation in Drosophila tissue culture cells.

In a permanent cell line derived from Drosophila embryos, cytoplasmic actin is produced as an unstable precursor, which is subsequently converted to a stable form. This conversion results in a reduction in isoelectric point, with no apparent change in molecular weight. The conversion involves an enzymatic acetylation, and results in an insensitivity to aminopeptidase digestion, suggesting N-terminal blockage. Both the acetylated and unacetylated actins can participate in the assembly of F-actin, but with different efficiencies.

Acetylation↗