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Biomedical subjects

E Cutz

Publications and source records attributed to E Cutz.

At least 73 records · Page 4Linked to original sources
PubMed1995

Acute cytomegalovirus infection in a child with Ménétrier's disease.

The cause of Ménétrier's disease is unknown, although allergic, autoimmune, and infectious, particularly viral, causes have been postulated. This case report describes a 3-year-old child with Ménétrier's disease in whom evidence of acute cytomegalovirus (CMV) infection was found. To our knowledge, this is the first case with evidence of acute infection, indicated by the presence of CMV-specific immunoglobulin M antibody in the acute serum as well as a seroconversion to CMV. CMV was also found in a gastric mucosal biopsy specimen using monoclonal antibodies to the early antigen of CMV.

Acute Disease↗
PubMed1995

Pulmonary neuroendocrine cells in neonatal rats with congenital diaphragmatic hernia.

Lung hypoplasia and persistent pulmonary hypertension are the principal causes of high mortality and morbidity in infants with congenital diaphragmatic hernia (CDH). Amine- and peptide-producing pulmonary neuroendocrine cells (PNEC), widely distributed throughout the airway mucosa, are thought to play an important role in both pulmonary development and regulation of pulmonary vascular tone. Furthermore, recent studies show increased levels of calcitonin gene-related peptide (CGRP), a pulmonary vasodilator produced by PNEC, during chronic hypoxia. The article reports data on morphometric analysis of CGRP immunoreactive PNEC clusters (neuroepithelial bodies, NEB) in a rat model of CDH. CDH was induced in neonatal Sprague Dawley rats by oral administration of 2,4-dichloro-phenyl-p-nitrophenylether (Nitrofen; Rohm Haas, Philadelphia, PA) to the mother at 10 days of gestation. Sections of lungs from term neonatal rats with and without CDH and controls were immunostained for CGRP (marker of NEB) with specific antibody against rat CGRP. NEB size and number of NEB/area of lung were assessed using a semiautomatic image analysis system. In lungs of neonatal rats with CDH, the number of NEB per surface area of lung parenchyma was significantly increased compared with the age-matched controls. Although the mean size of NEB was larger in CDH, the differences were not significant. This is the first study of PNEC in CDH. Whether the phenomenon observed in this study results in altered NEB function including imbalance in vasoactive mediators requires further studies, especially in the human being.

Animals↗
PubMed1995

Passive smoking is a risk factor for esophagitis in children.

A case-control study was undertaken to determine whether esophagitis in children correlated with exposure to parental cigarette smoking. At least one parent smoked in 77 (79%) of 97 families in the study group, compared with 42 (38.9%) of the 108 families in the control group (p < 0.001). Passive smoking is a risk factor for the development of esophagitis in children, providing added support for public health efforts to restrict childhood exposure to tobacco smoke.

Biopsy↗
PubMed1995

Increased respiratory system resistance and bronchial smooth muscle hypertrophy in children with acute postoperative pulmonary hypertension.

Following surgery for congenital heart disease, there is often an increased reactivity of the pulmonary vasculature to stimuli, resulting in rapid increases in pulmonary artery pressure and a clinical impression of stiff lungs. Lung mechanics were measured in 30 children, mean age 6.7 +/- 4.1 mo, who were ventilated and had pulmonary artery pressure monitoring following surgery for congenital heart disease. A group of 15 patients developed postoperative pulmonary hypertension. In these patients, respiratory system resistance was 43% higher (p = 0.001) and compliance 11% lower (p = 0.004) during acute pulmonary hypertension compared with baseline pulmonary artery pressure. No changes in resistance or compliance were seen in the 15 patients who did not develop pulmonary hypertension. The changes in lung mechanics interfered with mechanical ventilation, resulting in a 9.4% rise in PaCO2 during pulmonary hypertension. The bronchial smooth muscle was found to be increased by 68%, and the vascular smooth muscle was more than twice normal in lung biopsies from 9 pulmonary hypertension patients compared with 6 age-matched postmortem controls patients who had no cardiac or pulmonary disease. The bombesin-immunoreactive pulmonary neuroendocrine cells (PNEC) were also increased in the pulmonary hypertension patients. These findings suggest a coconstriction and cohypertrophy of bronchial and vascular smooth muscle during pulmonary hypertension. Mediators, such as bombesin, endothelin-1, and serotonin, are known to be produced by PNEC and may be involved in the observed vasoconstriction, increased respiratory system resistance, and smooth muscle hypertrophy.

Acute Disease↗
PubMed1995

Metered-dose inhaler salbutamol-induced tracheal epithelial lesions in intubated rabbits. Effects of the site of administration and time.

STUDY OBJECTIVES: To determine (1) whether metered-dose inhaler (MDI) salbutamol administered at the elbow connector of the anesthetic circuit produced tracheal epithelial lesions in intubated rabbits, and (2) the time course for resolution of tracheal lesions produced by MDI salbutamol through an intratracheal catheter. DESIGN: Prospective, randomized, controlled trial. SETTING: University-affiliated animal research laboratory. PARTICIPANTS: Thirty-nine adult New Zealand white rabbits. INTERVENTIONS: (1) Twenty-one intubated rabbits received 0,5, or 20 puffs of MDI salbutamol delivered at the elbow connector of the anesthetic circuit. (2) Eighteen intubated rabbits received five puffs of MDI salbutamol through an intratracheal catheter and were killed 1 h, 24 h, or 1 week later. MEASUREMENTS: Samples of trachea, bronchi, and lungs were examined by light microscopy, and the degree of epithelial injury was assessed semiquantitatively. RESULTS: MDI salbutamol (5 or 20 puffs) administered at the elbow did not induce tracheal epithelial injury. When administered through an intratracheal catheter, MDI salbutamol (five puffs) produced moderate or severe tracheal epithelial injury in those killed 1 h after the study. Evidence of epithelial regeneration was observed 24 h after the injury and recovery was virtually complete by 1 week. CONCLUSION: Epithelial lesions do not occur when the MDI salbutamol (5 or 20 puffs) is administered at the elbow connector of the ventilation circuit. Tracheal epithelial lesions produced by MDI salbutamol (five puffs) administered through an intratracheal catheter resolve within 1 week of the injury.

Albuterol↗
PubMed1994

Detection of calcitonin gene expression in human infant and monkey carotid body chief cells by in situ hybridization.

Calcitonin mRNA was detected in human and monkey carotid bodies by in situ hybridization histochemistry, using a 35S-labeled oligonucleotide probe for human calcitonin. In both human and monkey carotid body, moderate to high hybridization signal for calcitonin mRNA was observed in all cases. The hybridization signal in the formalin-fixed, paraffin-embedded samples was comparable to that obtained from frozen paraformaldehyde-fixed tissue. Our observations extend the finding of calcitonin-like immunoreactivity in the carotid body chief cells and indicate that calcitonin is produced in the carotid body, probably in the chief cells.

Animals↗
PubMed1994

Association of gastric metaplasia and duodenitis with Helicobacter pylori infection in children.

Helicobacter pylori infection causes chronic-active gastritis and is associated with peptic ulceration. However, the link between gastric H pylori colonization and duodenal ulcers is not well understood. Therefore, a retrospective, case-controlled study was conducted to determine whether H pylori infection is associated with gastric metaplasia and mucosal inflammation in the duodenum. Biopsy specimens from the duodenal bulb were obtained from 31 of 47 children with H pylori-induced gastritis. Two control groups, matched for age and sex, consisted of 33 children with normal antral histologic evaluation and 33 with H pylori-negative gastritis. Coded duodenal sections were stained with periodic acid-Schiff, hematoxylin-eosin, and silver to examine for gastric metaplasia, mucosal inflammation, and Helicobacter-like organisms, respectively. Thirteen of 31 (42%) H pylori-infected children had gastric metaplasia, in contrast to 1 of 33 with normal histologic characteristics (P < .0001) and 2 of 33 with H pylori-negative gastritis (P < .001). H pylori was detected overlying ectopic gastric mucosa in only 2 of 13 cases. Duodenal ulcers were identified endoscopically in 10 of 13 children with gastric metaplasia and 9 of 18 H pylori-infected subjects without metaplasia (P = NS). Twenty-four of 31 (77%) children with H pylori gastritis had duodenitis compared with 4 of 33 (12%) with H pylori-negative gastritis (P < .001) and 2 of 33 (6%) with a normal antrum (P < .001). Duodenitis was present in 14 of 19 children with H pylori infection and duodenal ulcers and 10 of 12 infected patients without mucosal ulceration (P not significant). These findings demonstrate a higher frequency of both gastric metaplasia and mucosal inflammation in the proximal small intestine of H pylori-infected children. However, there was a lack of correlation between the presence of duodenal ulceration and both gastric metaplasia and duodenitis.

Adolescent↗
PubMed1994

Proximate delivery of a large experimental dose from salbutamol MDI induces epithelial airway lesions in intubated rabbits.

The delivery of aerosolized drugs by metered dose inhaler (MDI) to intubated patients can be substantially improved by actuating the MDI through a narrow catheter placed inside the tracheal tube. However, the deposition of increased quantities of drug, surfactant, in particular oleic acid, and chlorofluorocarbon propellants on the lung surface could result in adverse effects not observed after oral MDI administration. To investigate this hypothesis, 42 adult intubated rabbits (six groups, n = 6 to 9/group) received Ventolin MDI, Ventolin placebo, a placebo MDI containing lecithin as surfactant, instilled salbutamol sulfate, instilled oleic acid solution, or no treatment (control). Heart rate, invasive blood pressure, and hemoglobin oxygen saturation, recorded continuously for the 3-h experiment, were unchanged from baseline (awake) values. Sections of trachea and lungs were reviewed blindly and graded using a four-point, nine-variable Ophoven scale. Blood was obtained after either 1 puff or 20 puffs MDI salbutamol to determine the pharmacokinetic profile of salbutamol. Multiple doses of both Ventolin and Ventolin placebo aerosols produced significant lesions to the epithelium of the trachea and main bronchi (p < 0.05). The histologic injury after lecithin placebo or salbutamol solution did not differ significantly from control, and all were significantly less than that observed after Ventolin MDI administration. Instilled oleic acid caused gross airway lesions. Maximum serum concentrations of salbutamol were 4.4 +/- 1.8 ng/ml after 1 puff and 419 +/- 168 ng/ml after 20 puffs. After 20 puffs, the total body clearance of salbutamol was 108 +/- 27 ml/min/kg, volume of distribution was 3.6 +/- 1.8 L/kg, and the elimination half-life was 22 +/- 7 min.(ABSTRACT TRUNCATED AT 250 WORDS)

Albuterol↗
PubMed1994

Simultaneous detection of messenger ribonucleic acids for bombesin/gastrin-releasing peptide and its receptor in rat brain by nonradiolabeled double in situ hybridization.

BACKGROUND: To simultaneously detect gene expression for bombesin/gastrin-releasing peptide (GRP) and its receptor in routinely processed tissue sections, we developed a protocol for non-radioactive double in situ hybridization (ISH) method. EXPERIMENTAL DESIGN: We used digoxigenin-labeled cRNA probe for GRP and a biotinylated cRNA probe for GRP-receptor (GRP-R) on frozen and/or formalin-fixed, paraffin-embedded sections of rat brain. The probes were applied singly and mixed (double ISH) and the signals visualized with two distinct chromogens. Antidigoxigenin-alkaline-phosphatase conjugate and nitro blue tetrazolium, producing a blue color reaction, was used to visualize GRP mRNA, and for GRP-R mRNA, avidin-alkaline phosphatase and vector red, were used resulting in a vivid red color. To unmask the signals on formalin-fixed, paraffin-embedded tissue, the sections were pretreated with proteinase VIII. RESULTS: Strong specific signals for GRP and/or GRP-R were detected in rat-brain neurons. The localization and intensity of the signal was comparable on frozen and routinely processed sections, although the latter showed better cytology and resolution. The overall distribution of GRP and GRP-R mRNAs in rat brain was similar to that previously reported with single ISH using radioactive-labeled probes. Double ISH revealed colocalization of the two mRNAs in some neurons with the expression of GRP mRNA often coexpressed with GRP-R mRNA. However, the expression of GRP-R mRNA did not always correlate with GRP mRNA signal. CONCLUSIONS: The nonradioactive, double ISH method is a relatively simple and sensitive procedure applicable to routinely processed tissues. This method may be suitable for studies on temporal and spacial distribution of peptide(s) and peptide receptor gene expression in health and disease.

Animals↗
PubMed1993

Oxygen sensing in airway chemoreceptors.

Pulmonary neuroepithelial bodies, composed of innervated clusters of amine- and peptide-containing cells, are widely distributed throughout the airway mucosa of human and animal lungs. Structurally, neuroepithelial bodies resemble chemoreceptors (such as carotid body, taste buds) and are thought to function as hypoxia sensitive airway sensors. Evidence for this is indirect, however, and the mechanism of oxygen sensing by these cells is unknown. Here we culture neuroepithelial bodies isolated from rabbit fetal lungs and identify voltage-activated potassium, calcium and sodium currents using the whole-cell patch clamp technique. Upon exposure to hypoxia there is a reversible reduction (25-30%) in the outward potassium current, with no change in inward currents. In addition, we demonstrate the expression of an oxygen-binding protein (b-cytochrome, NADPH oxidase) on the plasma membrane of these cells. The identification of an oxygen-sensing mechanism (namely the presence of an O2-sensitive potassium channel coupled to an O2 sensor protein) in the cells of pulmonary neuroepithelial bodies indicates that they are transducers of the hypoxia stimulus and hence may function as airway chemoreceptors in the regulation of respiration.

Animals↗
PubMed1993

An overview of culture and isolation methods suitable for in vitro studies on pulmonary neuroendocrine cells.

Successful isolation and culture of pulmonary neuroendocrine cells (PNEC) is essential for the investigation of cellular and membrane properties of these cells. Such studies are important to define the functional role for PNEC but are hampered by their scant numbers and widespread distribution within the pulmonary epithelium. Several in vitro methods for the isolation and culture of these cells have been described over the past decade, including organ culture, isolation of single cell suspensions enriched for PNEC, and immunomagnetic cell separation techniques. This paper reviews the various methods and discusses their advantages and pitfalls.

Animals↗
PubMed1993

Cell biology of pulmonary neuroepithelial bodies--validation of an in vitro model. I. Effects of hypoxia and Ca2+ ionophore on serotonin content and exocytosis of dense core vesicles.

Pulmonary neuroendocrine (NE) cells including the innervated clusters of NE cells--neuroepithelial bodies (NEB)--are difficult to study because of their small numbers and diffuse distribution within the airway mucosa of the lung. We have previously reported a method for isolation and culture of NE cells from rabbit fetal using a combination of mechanical and enzymatic dissociation followed by gradient centrifugation. This method provides single cell suspension of mixed lung cells enriched in NE cells, particularly those originating from NEB. This study further validates our in vitro model by detailed morphologic characterization of cultured NEB cells using high resolution light microscopy, transmission and scanning electron microscopy, HPLC for detection of serotonin (5-HT), and molecular (Northern blot) analysis of mRNA encoding for 5-HT synthesizing enzymes, tryptophane hydroxylase, and aromatic L-amino acid decarboxylase. In addition the effects of hypoxia on NEB cells in vitro were investigated to define the role of these cells as possible airway chemoreceptors. Exposure of NEB cultures to hypoxia resulted in decreased intracellular content of 5-HT accompanied by increased exocytosis of dense core vesicles (DCV). The amount of 5-HT release correlated with the degree of hypoxia, suggesting modulation by ambient pO2 levels. The role of Ca2+ ions in exocytosis of DCV and 5-HT release from NEB cells was tested in experiments with Ca2+ ionophore (A23187). Exposure of cultures to 5 micrograms/ml of ionophore resulted in up to 40% reduction in 5-HT content of NEB cultures as well as increased exocytosis of DCV. Our overall findings are consistent with a view that NEB cells are chemosensory in nature and that Ca2+ signaling pathway is involved in stimulus-secretion coupling. Further refinements in cell separation and culture methodology are required before more detailed investigation of NEB cell membrane properties, signal transduction mechanisms, and intracellular signaling pathways can be carried out.

Animals↗
PubMed1993

Paracrine effects of bombesin/gastrin-releasing peptide and other growth factors on pulmonary neuroendocrine cells in vitro.

Pulmonary neuroendocrine cells (PNEC) are numerous in the fetus where they have been implicated to have a role in fetal lung development. We assessed the effects of putative growth factors, gastrin releasing peptide (GRP), cholecystokinin (CCK), gastrin (GN), serotonin (5-HT), and epidermal growth factor (EGF), some of which are produced by PNEC, either alone or in combination, on cultured fetal rabbit PNEC from 20, 24, and 28 day fetuses. GRP increased the total protein of the cultures over a 7 day period in an age-dependent manner, with greatest effect in cultures from the 24 day fetus, no effect with the 28 day fetus, and an inhibitory effect on 20 day cultures. This was accompanied by an increase in PNEC, which could be blocked by treatment of the cultures with a monoclonal antibody to GRP (2A11). There was no increase in 3H-thymidine labeling of PNEC in GRP treated cultures but an increase in numbers of cells partially stained for 5-HT, suggesting the induction of a precursor cell. Other growth factors had neither an inhibitory nor a stimulatory effect either alone or in combination with GRP. Preliminary studies with 125I-GRP receptor localization suggests that the GRP receptor is mostly expressed on pulmonary fibroblasts, and less on epithelial cells, so that the role for GRP in fetal lung development, at least in the rabbit, is probably indirect, acting via a paracrine mechanism.

Animals↗
PubMed1993

Localization of cholecystokinin-like peptide in neuroendocrine cells of mammalian lungs: a light and electron microscopic immunohistochemical study.

We report immunohistochemical localization of cholecystokinin (CCK)-like immunoreactivity at the light and electron microscopy (EM) level in pulmonary neuroendocrine (NE) cells of human and other mammals (monkey, rabbit, rat, hamster, pig, dog and lamb). In addition, immunolocalization of CCK-like peptide was compared with that of bombesin (predominant peptide in human lung) and serotonin (an amine found in NE cells of most species). While CCK-like and serotonin-like immunoreactivity were identified in both solitary NE cells and NE cell clusters (neuroepithelial bodies, NEB) of all species studied, bombesin-like immunoreactive NE cells were found in human and monkey lungs only. The distribution and intensity of immunostaining for CCK-like peptide varied between species with some showing relatively high levels of expression (e.g., monkey, piglet, dog and lamb), others intermediate (human, rabbit) or weak immunostaining (rat, hamster). At the EM level, CCK-like immunoreactivity was localized in dense-core vesicles (DCV), the expected site of peptide storage. Using a double immunolabeling technique, CCK and serotonin were colocalized in some, but not all DCV. The potential role of CCK in the lung (or for other pulmonary peptides) may include a variety of functions such as modulation of bronchial or vascular tone, growth factor-like and/or hormonal effects.

Animals↗