PubMed Health⌕ Search

Biomedical subjects

C C Barnett

Publications and source records attributed to C C Barnett.

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

Jack A. Barney Resident Research Award winner. The inflammatory profile of interleukin-6, interleukin-8, and soluble intercellular adhesion molecule-1 in postinjury multiple organ failure.

BACKGROUND: Interleukin-6 (IL-6), interleukin-8 (IL-8), and adhesion molecules have been implicated as mediators in neutrophil (PMN) and endothelial cell (EC) interactions leading to postinjury multiple organ failure (MOF). Our hypothesis was that circulating levels of IL-6, IL-8, and soluble intercellular adhesion molecule-1 (sICAM-1) would discriminate patients at risk for postinjury MOF. METHODS: Serial plasma levels of IL-6, IL-8, and sICAM-1 were measured in 27 high-risk trauma patients. RESULTS: The IL-6 and IL-8 levels were significantly elevated in MOF patients compared with non-MOF patients at 12 and 36 hours postinjury. The IL-6 level was also elevated at 84 and 132 hours, and IL-8 at 84 hours. The sICAM-1 level did not become elevated in MOF patients until 132 hours postinjury. CONCLUSION: Interleukin-6 and IL-8 are elevated early after trauma and discriminate patients who will develop MOF. Late elevation of sICAM-1 likely results from PMN cytotoxicity leading to EC injury or inflammation.

Adult↗
PubMed1996

Soluble intercellular adhesion molecule-1 provokes polymorphonuclear leukocyte elastase release by CD18.

BACKGROUND: Elevated levels of soluble intercellular adhesion molecule-1 (sICAM-1) correlate with the development of postinjury multiple organ failure. Soluble ICAM-1 secretion is known to be induced in endothelial cells and monocytes by diverse inflammatory stimuli. We have found that incubation of quiescent polymorphonuclear leukocytes (PMNs) with sICAM-1 elicits elastase release and, more recently, that cross-linking CD18 receptors on PMNs also produces elastase release. Consequently, our study hypothesis was that sICAM-1 provokes PMN elastase release through its interaction with CD18. METHODS: To obtain sICAM-1, Chinese hamster ovarian cells transfected with human ICAM-1 were lysed and centrifuged at 150,000 g for 1 hour; the supernatant was passed over an ICAM-1 affinity column, eluted with 0.1 mmol/L glycine HCl, and concentrated with dialysis filter. Human PMNs (2.5 x 10(5)) were saturated with specific monoclonal antibodies for the beta 2 subunits (CD11a, CD11b, CD18) or nonspecific monoclonal antibodies for 30 minutes on ice before a 1-hour incubation with sICAM-1 (75 ng/ml) at 37 degrees C. Elastase activity was measured by the cleavage of n-methoxysuccinyl-A-A-P-V-p-nitroanilide. RESULTS: Neutrophil incubation with sICAM-1 resulted in 19.2% +/- 2.8% of total PMN elastase, compared with 2.4% +/- 0.5% in the controls. Blockade of CD18 abrogated sICAM-1 provoked elastase release with monoclonal antibodies to CD18 (TS1/18, 31H8) resulting in 4.3% +/- 1.0% and 5.5% +/- 1.4% elastase release, respectively. Blockade of CD11a, CD11b, and nonspecific antibody controls had no effect on sICAM-1 induced elastase release. CONCLUSIONS: In vitro, sICAM-1 provokes PMN elastase release through CD18. This may represent a mechanism by which elevated levels of circulating sICAM-1, released from local injury sites, provoke distal organ dysfunction.

Animals↗
PubMed1996

Interleukin-6 delays neutrophil apoptosis via a mechanism involving platelet-activating factor.

BACKGROUND: Interleukin (IL)-6, an integral mediator of the physiologic acute phase response to injury, has been associated with adverse postinjury complications when present in excessive concentrations. The precise role of IL-6 is unclear, but may involve exacerbation of polymorphonuclear neutrophil leukocytes (PMN)-mediated hyperinflammation. We have shown that IL-6 delays PMN apoptosis, thereby inhibiting the resolution of inflammation. More recently we have found that IL-6 stimulates PMNs to generate platelet-activating factor (PAF). Given the evidence for PAF involvement in postinjury hyperinflammation, we hypothesized that IL-6 delayed apoptosis via a mechanism involving PAF. METHODS: PMNs were isolated from healthy human donors using plasma-Percoll gradients and were cultured in enriched RPMI 1640 media at 2 x 10(7) PMNs/mL for 24 hours (37 degrees C, 5% CO2). Subgroups were treated with IL-6 (0.1-10 ng/mL) or PAF (0.1-10 ng/mL) or pretreated with the PAF receptor antagonist WEB 2170 (20 microM) before IL-6 or PAF. Morphologic assessment and quantitation of apoptosis was performed with acridine orange/ethidium bromide stain. RESULTS: Both IL-6 and PAF suppressed PMN apoptosis. Pretreating PMNs with WEB 2170 abrogated the effects IL-6 as well as PAF. CONCLUSION: Interleukin-6 delays PMN apoptosis via a mechanism involving PAF. These observations may help elucidate the mechanisms of IL-6 and PAF in mediating postinjury hyperinflammation and secondary organ dysfunction, ultimately leading to effective therapeutic targets in patients at risk for multiple organ failure.

Apoptosis↗
PubMed1996

Laparotomy and proximal gastric vagotomy in Zollinger-Ellison syndrome: results of a 16-year prospective study.

OBJECTIVE: Pharmacological control of gastric acid hypersecretion in the Zollinger-Ellison syndrome has steadily improved, but medical treatment does not address the underlying tumor. The objective of this study was to evaluate the long-term effectiveness of a surgical approach to both tumor and acid hypersecretion in 22 patients with the Zollinger-Ellison syndrome. METHODS: Patients underwent laparotomy to resect tumors, combined with vagotomy to reduce acid secretion, followed by postoperative antisecretory therapy, if necessary. RESULTS: No surgical mortality or serious morbidity occurred. Tumor was found at laparotomy in nine patients (41%) and during long-term follow-up in an additional two patients (9%). Ten-year survival is 81%, with a long-term cure rate of at least 14%. Most patients (86%) have had long-term inhibition of acid secretion. Eight patients have discontinued regular use of acid-inhibiting medications. Patients requiring medication need less of it, and they have an improved acid inhibitory response to medication for up to 16 yr after surgery. CONCLUSION: Cure of the Zollinger-Ellison syndrome is possible in a minority of patients. Acid secretion can be safely reduced in almost all patients with laparotomy/vagotomy, usually allowing discontinuation, or reduced dose, of acid-inhibiting drugs. Long-term survival and quality of life are generally excellent.

Adolescent↗
PubMed1996

Neutrophil priming and activation in the pathogenesis of postinjury multiple organ failure.

The continuing study of multiple organ failure (MOF) has led to the development of inflammatory models of tissue injury in contrast to earlier infectious models. This change of focus is in response to more recent clinical observations suggesting that postinjury MOF frequently occurs in the absence of infection. In the alternative "two-hit" inflammatory model that has been proposed, the initial traumatic insult "primes" the inflammatory response such that a delayed, otherwise innocuous, inflammatory insult triggers an exaggerated response. The neutrophil (PMN), being uniquely equipped to cause oxidative tissue injury via the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase system, has been implicated as an early pivotal player in this model of postinjury MOF. Similar to the "two-hit" inflammatory model, circulating PMNs respond to proinflammatory mediators by becoming primed for enhanced superoxide anion (O2.) production and by increasing adherence to endothelium of organs that are susceptible to PMN-mediated injury. Subsequent proinflammatory insults promote further neutrophil sequestration and activate them for enhanced release of O2.-. The resulting tissue injury can be perpetuated and lead to eventual end-organ damage and failure. In terms of the NADPH oxidase system, PMN priming and activation by various agonists have been well documented in vitro and lead to increased endothelial damage. PMN priming and activation are also operable in an in vivo model of gut ischemia/reperfusion, a surrogate of shock and trauma resuscitation, leading to distant organ damage. Finally, in clinical studies of severely injured trauma patients, PMN priming and activation sequences identify patients at risk for developing MOF with its associated high mortality. Further characterization of the mechanisms that regulate PMN priming and activation in the trauma patient is necessary for the development of new therapeutic interventions designed to block deleterious PMN responses which lead to MOF while not compromising beneficial PMN functions of host defense and tissue repair.

Animals↗
PubMed1995

Interleukin-6 suppression of neutrophil apoptosis is neutrophil concentration dependent.

Apoptosis of polymorphonuclear leukocytes (PMNs) is a critical step in the resolution of tissue inflammation. PMN apoptosis has been studied extensively in vitro, and diverse inflammatory mediators have been shown to modulate the process. The reported effects of interleukin-6 (IL-6) on PMN apoptosis are inconsistent; however, analysis of published studies reveals at least one discriminating factor--the use of varied concentrations of PMNs in the experimental design. Consequently, we hypothesized that the in vitro effects of IL-6 on PMN apoptosis varied with the concentration of PMNs in culture. PMNs isolated from healthy human donors were cultured at concentrations from 1 to 20 x 10(6)/mL, and incubated with IL-6 doses from 1 to 100 ng/mL. PMNs cultured at 1-5 x 10(6)/mL were unaffected by IL-6; in contrast, IL-6 inhibited apoptosis in PMNs cultured at 10-20 x 10(6)/mL, compared with untreated similarly concentrated PMNs. These data suggest caution in interpreting in vitro studies of apoptosis; on the other hand, appropriately designed experiments may help elucidate the regulation of apoptosis in vivo.

Apoptosis↗
PubMed1995

Intercellular adhesion molecule-1 promotes neutrophil-mediated cytotoxicity.

BACKGROUND: Interaction of the CD11/CD18 complex on polymorphonuclear neutrophils (PMNs) and intercellular adhesion molecule (ICAM)-1 on endothelium is a critical event in PMN-mediated tissue injury. In addition, increased expression of ICAM-1 on type I pneumocytes has been identified in a variety of pulmonary disorders associated with PMN-induced inflammation. We hypothesized that ICAM-1 up-regulation is sufficient to promote cytotoxicity via activated PMNs. METHODS: The complementary DNA for human ICAM-1 was transfected into Chinese hamster ovarian (CHO) cells, which do not inherently express this adhesion receptor, by using the expression vector CD1.8. Fluorescence-activated cell sorter analysis revealed 62% CHO cell surface expression of ICAM-1. Wild type and transfected CHO cells were labeled with chromium 51 and exposed to quiescent or activated (1 mumol/L phorbol myristate acetate) PMNs for 4 hours. Subsets were pretreated with a monoclonal antibody to ICAM-1. PMN cytotoxicity was determined by specific percent 51Cr release. RESULTS: Incubation of quiescent PMNs with wild type and transfected CHO cells produced nominal cell lysis, 0.5% +/- 0.3% and 0.2% +/- 0.2%, respectively. Activated PMNs produced 13.6% +/- 3.2% versus 1.4% +/- 0.7% cell lysis, comparing transfected with wild type CHO cells, and 0.5% +/- 0.2% cell lysis after pretreatment with a monoclonal antibody to ICAM-1, p < 0.01. CONCLUSIONS: ICAM-1 up-regulation is sufficient to promote cytotoxicity via activated PMNs. This may represent a potential target for attenuating PMN-mediated injury to endothelial and other cell lines, including parenchyma.

Animals↗
PubMed1993

Acid secretion and serum gastrin in normal subjects and patients with duodenal ulcer: the role of Helicobacter pylori.

OBJECTIVES: To compare gastric secretory function in patients with duodenal ulcer and in healthy volunteers with and without Helicobacter pylori infection. METHODS: Basal acid output, peak acid output, meal-stimulated acid output, fasting and meal-stimulated serum gastrin concentrations were measured in 136 healthy volunteers (63 H. pylori positive, 73 H. pylori negative) and 52 duodenal ulcer patients, all but one of whom were H. pylori positive. RESULTS: By multivariate linear regression analysis, H. pylori infection was a significant negative predictor of basal acid output and a positive predictor of fasting and meal-stimulated gastrin concentrations. When compared to truly normal (i.e., H. pylori-negative) control subjects, duodenal ulcer patients had elevated basal acid output, peak acid output, fasting and meal-stimulated gastrin concentrations. CONCLUSIONS: Our results show that in patients with duodenal ulcer disease, hypergastrinemia is largely related to gastric H. pylori infection, whereas acid hypersecretion is due to factors other than H. pylori.

Adult↗
PubMed1991

Effect of age on gastric acid secretion and serum gastrin concentrations in healthy men and women.

The effects of age on basal, meal-stimulated, and human gastrin-17-stimulated gastric acid secretion rates and serum pepsinogen concentrations were evaluated in 41 healthy men and women. Older subjects (ages 44-71 years; mean, 57 years) had higher mean basal, meal-stimulated, and gastrin-17-stimulated acid secretory rates and basal serum pepsinogen I and II concentrations than younger subjects (ages 23-42 years; mean, 33 years). Age-related differences in acid secretion were especially prominent in men, and age-related differences in serum pepsinogen I and II concentrations were more prominent in women. Higher gastric acid secretion rates in older subjects could not be explained by body size (height, weight, body surface area, or fat-free body mass) or by the higher incidence of infection with Helicobacter pylori. Using a multivariate linear regression model, age had an independent positive effect on acid secretion, and H. pylori infection had an independent negative effect. It was concluded that aging is associated with an increase in gastric acid secretion in humans, especially in men, while infection with H. pylori is associated with lower acid secretion rates.

Adult↗
PubMed1991

Cloning and amplification of the gene encoding an extracellular beta-glucosidase from Trichoderma reesei: evidence for improved rates of saccharification of cellulosic substrates.

We have cloned and determined the nucleotide sequence of the gene encoding an extracellular beta-glucosidase (bgl1) from the cellulolytic fungus Trichoderma reesei. The predicted open reading frame of the bgl1 gene is interrupted by two putative introns of 70 and 64 bp and encodes a protein with a calculated molecular weight of 75,341. The genomic segment encoding bgl1 was cloned into a vector that contained the selectable marker gene, amdS. Transformation of T. reesei with this vector resulted in several stable transformant strains all possessing an increased copy number of the bgl1 gene integrated into the genome together with elevated rates of glucose production from avicel. One transformant produced an extracellular cellulase with a five-fold increase in the rate of production of glucose from cellobiose, a 33% rate increase from avicel, and a 17% increase from phosphoric acid swollen cellulose. These data suggest that the cellulolytic activity of T. reesei strains may be specifically improved by transformation with cloned cellulase genes.

Amino Acid Sequence↗
PubMed1990

Cloning, characterization, and expression of two alpha-amylase genes from Aspergillus niger var. awamori.

Using synthetic oligonucleotide probes, we cloned genomic DNA sequences encoding an alpha-amylase gene from Aspergillus niger var. awamori (A. awamori) on a 5.8 kb EcoRI fragment. Hybridization experiments, using a portion of this cloned fragment to probe DNA from A. awamori, suggested the presence of two alpha-amylase gene copies which were subsequently cloned as 7 kb (designated as amyA) and 4 kb (amyB) HindIII fragments. DNA sequence analysis of the amyA and amyB genes revealed the following: (1) Both genes are arranged as nine exons and eight introns; (2) The nucleotide sequences of amyA and amyB are identical throughout all but the last few nucleotides of their respective coding regions; (3) The amyA and amyB genes from A. awamori share extensive homology (greater than or equal to 98% identity) with the genes encoding Taka-amylase from A. oryzae. In order to test whether both amyA and amyB were functional in the genome, we constructed vectors containing gene fusions of either amyA and amyB to bovine prochymosin cDNA and used these vectors to transform A. awamori. Transformants which contained either the amyA- or amyB-prochymosin gene fusions produced extracellular chymosin, suggesting that both genes are functional.

Amino Acid Sequence↗
PubMed1989

The development of gene expression systems for filamentous fungi.

Filamentous fungi have been used for decades in the commercial production of enzymes, antibiotics, and specialty chemicals. Traditionally, improving the yields of these products has involved either mutagenesis and screening or modification of fermentation conditions. Generally, selective breeding of strains has not been successful, because most of the commercially important fungal species lack a sexual cycle. For a few species, strain improvements have been made possible by employing the parasexual cycle for genetic crosses (30). The recent development of DNA-mediated transformation systems for several industrially important fungal species has spawned a flurry of research activity directed toward the development of gene expression systems for these microorganisms. This technology is now a viable means for novel and more directed approaches to improving existing fungal strains which produce enzymes or antibiotics. In addition, fungal expression systems are now being tested for the production of heterologous gene products such as mammalian pharmaceutical proteins. The goal of this review is to present a summary of the gene expression systems which have recently been developed for some filamentous fungi of commercial importance. To insure that the most recent developments are presented we have included data from not only scientific papers, but also from personal communications, abstracts, symposia, and our own laboratory.

Journal Article↗
PubMed1987

Comparison of two antimuscarinic drugs, pirenzepine and propantheline, on gastric acid secretion, serum gastrin concentration, salivary flow and heart rate in patients with duodenal ulcer disease.

Effects of orally-administered pirenzepine and propantheline bromide on food-stimulated gastric acid secretion, serum gastrin concentration, salivary flow and heart rate were compared in 10 duodenal ulcer patients in a placebo-controlled, double-blind study. Pirenzepine inhibited acid secretion by 25, 36 and 44% at doses of 50, 100, and 150 mg, respectively, while propantheline inhibited acid secretion by 32 and 41% at doses of 15 and 45 mg, respectively. None of the doses of pirenzepine affected food-stimulated serum gastrin concentrations, whereas 45 mg propantheline increased serum gastrin concentration significantly above placebo control. Enhancement of gastrin release by propantheline was not due to its antisecretory effect since intragastric pH after the meal was held constant at 5.0 by intragastric titration in vivo. Pirenzepine had no significant effect on heart rate and little or no inhibitory effect on salivary volume, depending on the dose administered. By contrast, both doses of propantheline increased heart rate and reduced salivary volume significantly (P less than 0.05). Thus, pirenzepine and propantheline in the doses administered inhibited acid secretion to approximately the same extent but pirenzepine had fewer effects on other organs.

Adult↗
PubMed1986

Effect of doxepin on basal gastric acid and salivary secretion in patients with duodenal ulcer.

We compared the effect of 50- or 100-mg doses of oral doxepin or a placebo on basal gastric acid secretion, salivary flow, and pulse rate in seven asymptomatic patients with chronic duodenal ulcer disease. Acid secretion and salivary flow were measured for four 1-hour periods beginning at 3.5, 5.5, 7.5, and 9.5 hours after medication, with plasma sampling for measurement of doxepin at the midpoint of each collection period. Compared to placebo, the 50- and 100-mg doses of doxepin reduced mean basal acid output by 46% and 37%, respectively. There was no significant difference in the effect of the 50- or 100-mg dose on acid secretion even though mean plasma concentrations of doxepin were higher with the 100-mg than with the 50-mg dose (p less than 0.01). Salivary flow was reduced by 62% and 84% with the 50- and 100-mg doses, respectively, whereas doxepin had no effect on mean pulse rate.

Adult↗
PubMed1985

In vivo and in vitro evaluation of magnesium-aluminum hydroxide antacid tablets and liquid.

The effect of magnesium-aluminum hydroxide antacid tablets or liquid on food-stimulated gastric acidity was evaluated in vivo in eight duodenal ulcer patients. Experiments were performed also in vitro. Although in vitro neutralizing capabilities of the two preparations were the same (28.3 +/- 0.1 mmol/liter), the duration of effect of tablets was longer in vivo. For example, at 3 3/4 hr after an eaten meal, mean hydrogen ion concentration with three tablets was 29.8 +/- 9.9 mmol/liter while with 15 ml liquid it was 59.6 +/- 10.3 mmol/liter (P less than 0.05). Additional studies were performed in vitro to explain the longer duration of effect of tablets compared with liquid in vivo. These experiments suggested that tablets reacted more slowly with acid than did liquid and that saliva, which was mixed with tablets during chewing, also contributed to the prolonged duration of effect.

Aluminum Hydroxide↗
PubMed1985

Gastric bicarbonate secretion in patients with duodenal ulcer.

The gastric mucosa secretes both acid and bicarbonate. In patients with duodenal ulcers, gastric acid hypersecretion is well-established. However, gastric bicarbonate secretion rates in these patients have not been reported. Accordingly, we calculated gastric acid and bicarbonate secretion rates in 13 patients with duodenal ulcer and 13 healthy subjects (controls) using a recently validated method that uses measurements of gastric juice volume, acidity (hydrogen-ion concentration), and osmolality. Non-parietal and parietal gastric volume secretion were also calculated. Although ulcer patients secreted significantly more acid than controls under basal conditions and during a submaximal intravenous pentagastrin infusion, they secreted similar amounts of bicarbonate. Ulcer patients secreted significantly more parietal and nonparietal fluid than controls. Increased nonparietal secretions in duodenal ulcer patients diluted excessive, acidic parietal secretions, preventing significant differences in gastric acidity in ulcer patients and control subjects (50.1 +/- 8.7 vs. 44.0 +/- 9.7 mmol/L basally; 111.0 +/- 3.1 vs. 102.4 +/- 7.5 mmol/L during pentagastrin infusion, respectively). These studies indicate that gastric bicarbonate secretion is close to normal in patients with duodenal ulcer, whereas acid secretion from parietal cells and nonparietal volume secretion are greater than normal.

Adult↗
PubMed1981

Routine early endoscopy in upper-gastrointestinal-tract bleeding: a randomized, controlled trial.

To determine whether routine early endoscopy is beneficial to patients with upper-gastrointestinal-tract bleeding that ceases during hospitalization, we randomly assigned 206 patients to routine endoscopy (100 patients) or no routine endoscopy (106). Patients in the latter group underwent endoscopy only if recurrent bleeding occurred during hospitalization or if x-ray films disclosed gastric ulcer or suggested neoplasia. All patients were initially treated with an empiric antacid regimen. When the two groups were compared (experimental versus control), there were no significant differences in overall hospital deaths (11 versus eight), recurrence of bleeding (33 versus 32), number of transfusions required to treat recurrent bleeding (mean +/- S.E.M., 7.4 +/- 1.2 versus 6.3 +/- 0.7 units), deaths after recurrent bleeding (eight versus five), or duration of hospital stay. During the 12 months after discharge, there were also no significant differences in frequency of readmission to the hospital, incidence of further gastrointestinal bleeding, number of hemorrhage-related deaths, or frequency of gastrointestinal surgery. We conclude that endoscopy should not be a routine procedure in patients with upper-gastrointestinal-tract bleeding that ceases during treatment.

Clinical Trials as Topic↗