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S Nelson

Publications and source records attributed to S Nelson.

At least 199 records · Page 11Linked to original sources
PubMed1994

CD4+ T lymphocyte depletion attenuates lipopolysaccharide-induced tumor necrosis factor secretion by alveolar macrophages in the mouse.

Mechanisms underlying the control of cytokine secretion by alveolar macrophages are not fully understood. We hypothesized that T lymphocytes or their products modulate the capacity of alveolar macrophages to release cytokines in response to an exogenous stimulus. In this study, we investigated the role of lymphocytes expressing surface CD4 (CD4+) antigen in the regulation of tumor necrosis factor alpha (TNF-alpha) secretion by alveolar macrophages. Specific pathogen-free male BALB/c mice were injected intraperitoneally with 0.3 mg monoclonal anti-CD4 antibody or phosphate-buffered saline. Depletion of CD4+ splenic lymphocytes was confirmed 6 days later by flow cytometry. On day 6, mice were challenged intratracheally with E. coli lipopolysaccharide (LPS, 1-100 micrograms/100 g BW) or phosphate-buffered saline. The lungs were lavaged 3 h later and the bronchoalveolar lavage fluid assessed for TNF activity and cell recovery (total and differential). No TNF was detected in the lavage fluid of animals pretreated with antibody or phosphate-buffered saline and given phosphate-buffered saline intratracheally. However, the saline-treated mice challenged with LPS (100 micrograms/100 g BW) released 3.76 +/- 0.18 ng TNF/ml bronchoalveolar lavage fluid. In contrast, mice depleted of CD4+ T lymphocytes released almost 50% less TNF (1.94 +/- 0.23 ng TNF/ml lavage fluid, p < 0.001) in response to the same dose of LPS.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Growth patterns of Labrador Inuit youth: II. Skeletal age.

Few studies have been conducted on skeletal maturity of circumpolar populations despite its importance as background knowledge to orthopedic and orthodontic procedures or for other medical problems involving endocrine disturbances. The purpose of this study was to compare skeletal age with chronological age of Labrador Inuit youth aged between 5-18 years and to compare these results with data from a national survey of United States youth. The sample included 32% (n = 100) of the Inuit youth living in Nain, Labrador, Canada (Male = 41, female = 59). Hand wrist radiographs, collected during a field study in 1991, were used to estimate bone age using the Greulich and Pyle bone specific method. The mean relative Inuit skeletal ages increased almost consistently with chronological age but showed considerable individual variation as shown by the 95% confidence intervals. The pattern of growth of skeletal vs chronological age was similar to the National Center for Health Statistics data but the tempo was slower. The Z-scores for mean male relative bone ages ranged from -0.7 to -1.9 and for females from -0.6 to -1.4. The results indicated that Inuit males started to reach adult skeletal maturity levels by the chronological age of 17 years 9 months, and Inuit females by 15 years 8 months. Generally, Inuit skeletal ages were delayed by 10-24 months behind the reference atlas skeletal ages and 9-22 months behind the Inuit chronological ages.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1994

Rapid preparation of plasma for 'Stat' coagulation testing.

We undertook to confirm and extend the previous work on the use of microcentrifugation (2 minutes at 11,000 g) to prepare platelet-poor plasma for assay of the prothrombin time, partial thromboplastin time, fibrinogen level, D-dimer, antithrombin III, and dilute Russell viper venom time. We compared results of routinely submitted blood samples by both high-speed and routine (15 minutes at 1800g) centrifugation. We found no significant differences in assay results and concluded that the high-speed technique is a reliable and useful option for minimizing turnaround times for these coagulation assays.

Blood↗
PubMed1993

Recombinant cytokines and pulmonary host defense.

The recent discovery of several cytokines and their purification using recombinant DNA technology has uncovered their role as critical factors in pulmonary host defense. The importance of tumor necrosis factor, interferon-gamma, and granulocyte-colony stimulating factor in lung infections was first elucidated in animal models and has been confirmed with neutralization studies. This article reviews these three cytokines, their recent use in human subjects, and their potential use in the future.

Animals↗
PubMed1993

Tumor necrosis factor-alpha inhibits endothelium-dependent relaxation.

Tumor necrosis factor-alpha (TNF-alpha) stimulates nitric oxide (NO) in vascular endothelium by induction of the enzyme NO synthase II (NOS II). We examined the effects of TNF-alpha on 1) endothelium-dependent (EDR) and endothelium-independent (EIR) relaxation and 2) contraction of bovine intralobar pulmonary arteries (BPA) and veins (BPV) in vitro. Acetylcholine (ACh), bradykinin (BK), histamine, and A23187 produced EDR of BPA contracted with a 50% effective concentration of U-46619 (15 nM), because relaxation was abolished by endothelium-rubbing and attenuated by L-NG-mono-methylarginine (L-NMMA; 300 microM). TNF-alpha (0.00417, 0.0417, 0.417, and 1.25 micrograms/ml) incubated with BPA for 60 min inhibited EDR of the BPA to ACh, BK, and histamine. The effects of TNF required 30 min for onset. Recovery of EDR occurred 3-4 h after washout of TNF-alpha. Pentoxifylline (1 microM) did not affect ACh-induced EDR but selectively reversed TNF-alpha-mediated inhibition of ACh-induced EDR. TNF-alpha-mediated inhibition of EDR was not reversible by L-NMMA, an inhibitor of NOS I and NOS II, the cyclooxygenase inhibitor ibuprofen, or CV-3908 (1 microM), a platelet-activating factor antagonist. The inhibitory effect of TNF-alpha on EDR was not mediated by nonspecific sensitization of the endothelium to human protein because recombinant human granulocyte colony-stimulating factor (10, 50, and 500 x 10(3) U/ml) did not affect EDR of BPA. The effect of TNF-alpha was specific for release of NO from the endothelium of BPA because TNF-alpha did not affect 1) EDR of BPV to ACh, BK, or ATP; 2) EIR of BPA or BPV to nitroprusside; and 3) contraction of either BPA or BPV to KCl, U-46619, histamine, norepinephrine, or serotonin. Thus TNF-alpha appears to selectively inhibit receptor-mediated EDR and NO release in BPA. TNF-alpha-mediated inhibition of EDR differs from that of L-arginine-based inhibitors and may represent an endogenous physiological mechanism of regulation of NO in the endothelium.

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5↗
PubMed1993

Tumor necrosis factor inhibits stimulated but not basal release of nitric oxide.

Tumor necrosis factor alpha (TNF alpha) increases nitric oxide (NO) synthase in vascular endothelium, but it inhibits endothelium-dependent relaxation (EDR) of vascular smooth muscle. We tested whether TNF alpha inhibits the response to, or release of, NO in bovine pulmonary artery (BPA) using the technique of perfusion-superfusion bioassay and ozone chemiluminescence. Effluent from the perfused BPA with endothelium (donor)-relaxed endothelium-rubbed bovine coronary artery (BCA) (detector). Moreover, effluent from the donor stimulated with acetylcholine (ACh) or bradykinin (BK) (0.001 to 100 nmol) relaxed the detector. Direct application of these agonists to the detector failed to produce relaxation. Basal and agonist-stimulated effluent from the donor treated with L-NG-monomethylarginine (LNMMA) (100 microM) suppressed effluent-mediated relaxation of the detector. ACh and BK released LNMMA-inhibitable nitrite and nitrate from the BPA. Thus, the effluent contained NO. Exposure of the donor to TNF alpha (1.25 micrograms/ml) for 60 min did not affect basal release of NO, but it attenuated bioassayable and chemiluminescence-detectable NO release by ACh and BK. The inhibition of NO release was directly related to the magnitude of inhibition of EDR by ACh and BK. Thus, TNF alpha selectively inhibits receptor-mediated release of NO without affecting basal release of NO. This effect differs from that of L-arginine-based inhibitors of NO and represents a unique physiologic mechanism of regulation of NO in the endothelium.

Acetylcholine↗
PubMed1993

Alveolar macrophage release of tumor necrosis factor during murine Pneumocystis carinii pneumonia.

Tumor necrosis factor-alpha (TNF-alpha), a proinflammatory cytokine produced principally by mononuclear cells, is released in response to a variety of pulmonary pathogens. We hypothesized that release of TNF in the lung is a normal part of the host response to intratracheal challenge with Pneumocystis carinii. To test this hypothesis, we measured TNF in bronchoalveolar lavage fluid (BALF) in normal and CD4-depleted mice at various intervals in acute and chronically infected animals. To assess the cell of origin and the control of TNF release in the lung, we measured mRNA for TNF by a competitive polymerase chain reaction and assessed the capacity of adherence-enriched cells to produce TNF in vitro in response to lipopolysaccharide. Our data demonstrate that TNF peaks at 3 h in both control and CD4-depleted mice after acute challenge with P. carinii and this increase in TNF precedes the influx of inflammatory cells into the lung. TNF levels in BALF return to undetectable levels by day 3. In chronically infected animals, there is a 5-fold increase in mRNA for TNF in adherent cells which is associated with an increased capacity to release TNF in vitro. These data suggest that TNF is a normal host response to P. carinii infection; however, there is no difference in acute TNF release between control animals that clear their infection and CD4-depleted animals that develop chronic infection. TNF is upregulated in chronically infected animals, but CD4 depletion results in the loss of additional host factors essential for resolution of this infection.

Animals↗
PubMed1993

Effects of halothane anesthesia on vasoconstrictor response to NG-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthesis, in sheep.

This study tests the hypothesis that halothane-induced inhibition of the endothelium-derived relaxing factor/nitric oxide (EDRF/NO) pathway significantly contributes to cardiovascular performance and thus reduces the vasoconstrictor response to NO synthesis inhibitors in vivo. We determined the effects of the administration of the NO synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in chronically instrumented, halothane-anesthetized sheep and in awake control animals. Six sheep underwent halothane anesthesia (1.5 vol%) with mechanical ventilation. Five sheep were studied in the awake state with spontaneous breathing. Both groups received a bolus of L-NAME (25 mg/kg), followed 4 h later by L-arginine (300 mg/kg) to reverse the effects of L-NAME. L-NAME administration caused a significant increase in pulmonary and systemic vascular resistance (P < 0.05) in both groups. However, L-NAME produced a sharp increase in mean arterial and pulmonary artery pressures only in the control group, whereas the pressor response in the halothane group was attenuated. Cardiac output, which was significantly lower after L-NAME administration in both groups, increased after L-arginine. The results suggest that halothane does not significantly alter the EDRF/NO-mediated effects on the vasculature but potentiates the cardiac depressant effect of L-NAME.

Anesthesia, Inhalation↗
PubMed1993

Tumor necrosis factor alpha inhibits contractions to sympathetic nerve stimulation by a nitric oxide-dependent mechanism.

Gram-negative sepsis and administration of tumor necrosis factor alpha (TNF alpha) are associated with hypotension and peripheral neuropathies suggestive of impaired sympathetic neurotransmission. We examined the effect of TNF alpha on the responses of the bovine pulmonary artery (BPA) to transmural sympathetic nerve stimulation (SNS). BPA contracted to SNS (0.5-32 Hz, 5-10 V, 2-msec duration, 2-msec delay) in a frequency-dependent manner. The contractions of the BPA to SNS were mediated by norepinephrine and activation of postsynaptic alpha 1-adrenoceptors, since they were attenuated by prazosin. Maximum contraction of the BPA to SNS was significantly enhanced (148 +/- 37% increase, n = 6) after inhibition of nitric oxide synthase with L-NG-monomethylarginine (LNMMA, 500 microM), an effect abrogated by L-arginine (1 mM). TNF alpha (0.0042, 0.042, and 0.42 micrograms/ml) selectively inhibited contractions of the BPA to SNS without affecting the contraction of the BPA to exogenous norepinephrine. In BPA incubated with LNMMA (5-500 microM), TNF alpha facilitated rather than inhibited SNS. TNF alpha increased the formation of amperiometrically measured free nitric oxide in bovine adrenal chromaffin cells in primary culture. The data show that in the absence of LNMMA, TNF alpha releases free nitric oxide from a sympathetic neuron and selectively inhibits the contractions of the BPA to SNS. In BPA in which nitric oxide synthase I is inhibited by LNMMA, TNF alpha amplifies the contractions to SNS, even in the absence of endothelium. Thus, TNF alpha can modify vascular smooth muscle tone by affecting SNS. TNF alpha inhibits SNS at the level of the neuron by a mechanism involving the L-arginine-nitric oxide pathway. TNF alpha-induced suppression of SNS and neurotransmission may contribute to the hypotension and peripheral neuropathy of sepsis.

Acetylcholine↗
PubMed1993

Downstream insertion of the adenovirus tripartite leader sequence enhances expression in universal eukaryotic vectors.

A series of universal eukaryotic gene expression vectors was constructed. All vectors contain a viral promoter and enhancer, a polylinker for insertion of the gene of interest and a polyadenylation sequence. To enhance translation, we inserted the tripartite leader sequence of an adenovirus downstream of the promoter. Using the chloramphenicol acetyl transferase (cat) gene as a marker, we show that the strength of various promoters/enhancers in different cell lines differed by two orders of magnitude. The presence of the tripartite leader increased the efficiency of gene expression up to 18-fold. The level of increase is promoter specific and is most likely influenced by additional sequences flanking the tripartite leader sequence.

3T3 Cells↗
PubMed1993

Long-term ethanol consumption alters the hepatic response to the regenerative effects of tumor necrosis factor-alpha.

The pathogenesis of chronic alcoholic liver disease is uncertain, but it may reflect an impaired wound healing response to ethanol-induced liver injury. Cell-to-cell communication such as that mediated by the cytokine tumor necrosis factor is necessary for successful liver regeneration and complete recovery from liver injury. Hence disruption of intercellular regenerative signaling may contribute to the pathogenesis of chronic alcoholic liver disease. To test this hypothesis, the cytokine and regenerative responses triggered by partial hepatectomy were compared in ethanol-fed rats and isocalorically maintained, pair-fed controls. To further clarify the effect of ethanol on tumor necrosis factor-modulated regenerative effects, we evaluated some of the rats in each feeding group after pretreatment with antibodies to tumor necrosis factor. As expected, ethanol inhibited DNA synthesis and liver cell proliferation after partial hepatectomy. Ethanol-associated inhibition of liver regeneration occurred despite apparently similar serum concentrations of the tumor necrosis factor-inducible cytokine interleukin-6. Treatment with antibodies to tumor necrosis factor 1 hr before partial hepatectomy inhibited post-partial hepatectomy induction of interleukin-6 and liver regeneration in ethanol-fed and pair-fed rats. However, serum interleukin-6 was reduced more in ethanol-fed rats than in control rats (93% vs. 66%; p < 0.05). Antibodies to tumor necrosis factor also inhibited hepatic DNA synthesis more in ethanol-fed rats than in controls (85% vs. 50%; p < 0.05). In ethanol-fed rats, the increased effect of tumor necrosis factor antibody on post-partial hepatectomy DNA synthesis suggests heightened sensitivity of hepatocytes to tumor necrosis factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1992

In vivo metabolic response of hepatic nonparenchymal cells and leukocytes to granulocyte-macrophage colony-stimulating factor.

This study investigates the in vivo glucose utilization of various immune-competent cells after an intra-arterial injection of a nonlethal dose (30 micrograms/kg body weight) of murine recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF). Injection of GM-CSF resulted in a rapid but transient reduction in the number of circulating neutrophils. After 20 min the number of neutrophils returned to normal values, and by 4 h it was about 80% greater than in time-matched saline-injected controls. One hour after the treatment, neutrophils were accumulated in the livers of GM-CSF-injected animals but not in control livers. In vivo glucose utilization by circulating neutrophils and mononuclear cells and various liver cell types was investigated by combining the 2-deoxyglucose tracer technique with cell isolation procedures. GM-CSF increased the in vivo glucose utilization of circulating and infiltrating neutrophils by more than 200%. Glucose utilization by circulating mononuclear cells was also doubled. After GM-CSF injection, glucose utilization by Kupffer cells was increased by 130% and by hepatic endothelial cells was increased by 60%. Indomethacin pretreatment blunted the hyperglycemia caused by GM-CSF injection; however, it did not inhibit the increased glucose utilization by immune-competent cells. This suggests that the effect of GM-CSF on glucose utilization by these cells is not mediated by prostanoids and is at least partially independent of the mass action of elevated glucose concentration. These findings indicate that GM-CSF may be an important member of the cytokine cascade that mediates the acute in vivo metabolic response of immune-competent cells in sepsis or endotoxemia.

Animals↗
PubMed1992

Contrasting effects of misoprostol on systemic and intrapulmonary lipopolysaccharide-induced tumor necrosis factor-alpha.

Tumor necrosis factor-alpha (TNF), a cytokine produced by mononuclear phagocytes in response to lipopolysaccharide stimulation, is a potent mediator of the inflammatory cascade. However, the immunomodulatory signals regulating TNF expression in the host are poorly defined. Recently, metabolites of the prostaglandin E series have been shown to inhibit TNF production in vitro. In order to determine if PGE1 alters TNF activity in vivo, rats were given misoprostol, a synthetic PGE1 analogue, or saline by gavage and subsequently challenged with either intravenous or intratracheal Escherichia coli lipopolysaccharide. These in vivo data show that PGE1 is a potent inhibitor of TNF production by systemic mononuclear phagocytes. In contrast, alveolar macrophages appear to be refractory to misoprostol's suppressive effects on LPS-induced TNF. This study supports in vitro observations that mononuclear phagocytes within different compartments exhibit differential responsiveness to immunomodulators.

Animals↗
PubMed1992

A new scale for assessing behavioral agitation in dementia.

The primary purpose of the present study was to develop a reliable and valid rating instrument for assessing treatment efficacy for behavioral problems in the cognitively impaired elderly. The Behavioral and Emotional Activities Manifested in Dementia (BEAM-D) Scale was developed for the operational assessment of troublesome and disruptive behaviors in dementia. Each behavioral category of the BEAM-D was clinically considered to be a significant deviation from normative behavior for the geriatric dementia patient. The reliability and validity of the BEAM-D was assessed in a group of 45 patients diagnosed with primary degenerative dementia. The mean interrater reliability of BEAM-D items was 0.90. Concurrent validity was established by comparison with currently used rating scales, the Brief Psychiatric Rating Scale (BPRS) and the Sandoz Clinical Assessment-Geriatric (SCAG). Stepwise regression analysis revealed that the items of the BEAM-D had a strong relationship with conceptually similar behavioral dimensions on the BPRS and SCAG.

Aged↗
PubMed1992

Epitope mapping of monoclonal antibodies to Torpedo acetylcholine receptor gamma subunits, which specifically recognize the epsilon subunit of mammalian muscle acetylcholine receptor.

Epitopes for four monoclonal antibodies (mAbs) to the gamma subunit of Torpedo nicotinic acetylcholine receptor (AChR), and one mAb crossreactive with the gamma and delta subunits of Torpedo AChR were mapped using overlapping synthetic peptides corresponding to the complete amino acid sequence of Torpedo gamma subunit. The epitopes for all mAbs were within a 50 residue sequence region, on the cytoplasmic surface of the AChR. Three mAbs crossreacted with mammalian muscle AChRs. Two of them specifically recognized the epsilon subunit of AChRs at adult neuromuscular junction. The epsilon-specific mAbs were used, in conjunction with mAbs specific for the alpha and beta subunits and anti-peptide antisera specific for the epsilon, gamma and delta subunits, to identify in Western blots the subunit complement of embryonic and adult bovine muscle AChRs.

Amino Acid Sequence↗
PubMed1992

Effect of granulocyte colony-stimulating factor on sepsis-induced changes in neutrophil accumulation and organ glucose uptake.

Neutropenia was seen in rats made septic by subcutaneous (sc) injection of Escherichia coli. The sepsis-induced increase in glucose uptake by tissues distant from the site of infection was not associated with increased myeloperoxidase (MPO) activity. Only the skin and muscle at the site of infection demonstrated an increase in both glucose uptake and MPO activity. Granulocyte colony-stimulating factor (G-CSF) attenuated the sepsis-induced decrease in circulating neutrophils. Both glucose uptake and MPO activity of skin and muscle adjacent to the infection site showed a smaller increase in G-CSF treated rats. In contrast, septic rats injected with G-CSF exhibited a greater number of leukocytes and a larger reduction in the number of bacteria in the sc lavage fluid. These results demonstrate that G-CSF is a potent immunomodulator that stimulates neutrophil function and also increases their recruitment to the site of infection, resulting in improved bacterial killing and host defense.

Animals↗
PubMed1992

Effect of pyocyanine, a pigment of Pseudomonas aeruginosa, on production of reactive nitrogen intermediates by murine alveolar macrophages.

In this study we investigated the effect of pyocyanine, a pigment produced by Pseudomonas aeruginosa, on production of reactive nitrogen intermediates by macrophages. We found that addition of pyocyanine to cultures of murine alveolar macrophages inhibited the capacity of these cells to produce reactive nitrogen intermediates (measured as nitrite) in a dose-dependent manner without altering cell viability, cytokine-induced Ia expression, or production of tumor necrosis factor.

Animals↗