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Biomedical subjects

L M Reid

Publications and source records attributed to L M Reid.

At least 91 records · Page 5Linked to original sources
PubMed1986

Regulation of insulin mRNA abundance and adenylation: dependence on hormones and matrix substrata.

The insulin mRNA levels of rat insulinoma cell lines increased six- to eightfold, and the cells entered a transient state of growth arrest when they were cultured in serum-free, hormonally defined medium and on an extract of extracellular matrix derived from a basement membrane-secreting tumor line, EHS. Insulinoma cultures in growth arrest responded to glucose with a two- to threefold increase in insulin secretion associated with an insulin mRNA that contained a poly(A) tail that was 120 to 140 bases longer than normal.

Adenoma, Islet Cell↗
PubMed1986

Effects of chronic in utero hypoxia on the pulmonary vasculature of the newborn guinea pig.

This report analyzes the effect on pulmonary vascular structure and function in the newborn guinea pig of chronic fetal hypoxemia, induced by maternal hypobaric hypoxia (380-420 torr) without direct interference with the utero-placental blood flow. Six pregnant guinea pigs were maintained in hypobaric chambers, 10 newborns from their litters being the hypoxic group. Twenty newborns from the litters of 10 pregnant guinea pigs maintained in air were the control group. After spontaneous delivery catheters were placed in the left carotid and the main pulmonary arteries of the newborns. Oxygen consumption was measured, pressures recorded from the pulmonary artery, right ventricle, and right atrium, oxygen saturation and hemoglobin concentration estimated on blood from systemic arteries, pulmonary artery, and right atrium, and cardiac output calculated (Fick principle). All data were normalized per kilogram body weight. Morphometric analysis of the pulmonary vasculature after injection of the pulmonary arteries showed no difference between the groups. Contrary to expectation chronic hypoxemia in utero did not cause pulmonary hypertension or the precocious muscularization of the precapillary unit found in human cases of persistent pulmonary hypertension: it caused growth retardation, a feature not typical of the human syndrome.

Animals↗
PubMed1986

Density gradient analysis of secretions produced in vitro by human and canine airway mucosa: identification of lipids and proteoglycans in such secretions.

Human and canine airway mucosal explants synthesize and secrete high molecular weight glycoconjugates, incorporating 14C-glucosamine, a radioactive precursor to epithelial glycoprotein. Our examination of secretions produced by several individual specimens, however, did not reveal epithelial glycoprotein of typical buoyant density (1.5 g/ml in CsBr); only a high-density component with features of glycoprotein and proteoglycan. To provide sufficient material for characterization, secretions from several specimens of human and canine explants were separately pooled and subjected to DGU in CsBr. After removal of lipids and proteins, the glycoconjugates were recovered into five fractions of different density. 14C-glucosamine had been incorporated in all five fractions. Fractions 1-4 together accounted for 88% of the radiolabel but gas chromatography indicated that none of these contained epithelial glycoprotein. Their amino acid compositions were similar to those of proteoglycans and electrophoresis confirmed the presence of chondroitin sulfates A, B, C, heparan sulfate and hyaluronic acid. Sugars typical of epithelial glycoprotein were identified only in the glycoconjugate subfraction 5 of lowest density (and also lowest in yield) in which glycosaminoglycans were also identified. By addition of radioactive precursors, 14C acetate, 14C palmitate and 14C mevalonic acid to the culture medium and autoradiography of the secreted lipids we have shown that the tracheal explants actively synthesize lipids. Lipids accounted for a high proportion, almost half by weight, of the explant secretion. While neutral and phospholipids predominate, glycolipids were also identified.

Amino Acids↗
PubMed1986

The platelet thromboxane inhibitor, dazmegrel, does not reduce monocrotaline-induced pulmonary hypertension.

Monocrotaline injures rat pulmonary endothelium, and pulmonary vascular remodeling, pulmonary hypertension, and right ventricular hypertrophy then develop. Platelets contribute to development of the pulmonary hypertension because platelet depletion 1 wk after monocrotaline administration reduces the right ventricular hypertrophy. To determine whether the platelet action is through thromboxane A2 generation, we administered the long-acting thromboxane synthetase inhibitor dazmegrel (UK-38,485) to rats receiving monocrotaline. Both before and after monocrotaline treatment, dazmegrel effectively (p = 0.01) reduced thromboxane release during clotting, platelets being the main source. We then studied 4 groups of rats: 1 group of rats received only monocrotaline as a single subcutaneous injection at 0 h; a second group received, in addition, dazmegrel in drinking water starting at -48 h, then daily until Day 21; a third group received only dazmegrel; a control group received no treatment. Dazmegrel did not prevent monocrotaline-induced growth retardation. Despite adequate intake and coverage of the critical period at approximately 1 wk after monocrotaline treatment, dazmegrel did not significantly prevent the development by Day 21 of right ventricular hypertrophy. On Day 21, platelet counts and plasma thromboxane B2 levels were similar in all 4 groups, suggesting no major platelet involvement at that time. It seems that the platelet contribution to pulmonary hypertension after monocrotaline treatment is not mediated by thromboxane A2.

Animals↗
PubMed1986

The pathology of obstructive and inflammatory airway diseases.

The diseases included are those commonly called chronic bronchitis, bronchiolitis, bronchiectasis and asthma. The definitions most commonly used are those called for and applied in epidemiological studies. In this symposium, it is the role of inflammation in these various diseases that will be explored. The term bronchiectasis describes bronchial or bronchiolar distortion and scarring. It is well described by the terms bronchitis obliterans and bronchiolitis obliterans. In the 'wet' form of the disease, chronic sputum production is a feature. The factors that cause mucus hypersecretion in chronic bronchitis probably operate. Chronic bronchitis is characterized by mucus hypersecretion. Recent studies reveal that change in the nature of secretion is an early sign: new constituents appear before the amount is appreciably increased. Bronchial aspirate from normal non-smoking human volunteers, as judged by density gradient ultracentrifugation, contained no typical epithelial glycoprotein but did contain a glycoconjugate of higher buoyant density that included sugars characteristic of proteoglycans. In normal volunteers who had smoked, albeit mildly, macromolecular yield was not increased; however, a glycoconjugate of buoyant density typical of epithelial glycoprotein but with sugars characteristic of both proteoglycans and glycoprotein was identified. In simple, chronic bronchitis a typical epithelial glycoprotein can be identified. Study of the canine model of chronic bronchitis supports these findings. In organ culture, human and canine airways do not secrete the typical epithelial glycoprotein under baseline conditions but they do when stimulated, as by cholinergic agents. Analysis of lipids also yields a similar picture in human disease and in the canine model. Cholesterol is typical of normal mucus. When secretion is obviously increased, glycolipid is also present.

Animals↗
PubMed1986

Extracellular matrix regulation of cell-cell communication and tissue-specific gene expression in primary liver cultures.

Epithelial-mesenchymal interactions are effected, in part, by extracellular matrix components. We have spent many years analyzing the influence of extracellular matrix, both as extracts of matrix and as purified matrix components, on the growth and differentiation of normal and neoplastic liver cells. Currently we are focused on analyzing the influence of the extracellular matrix components, glycosaminoglycans and proteoglycans. We have found that these factors induce dramatic morphological changes, are potent inducers of gap junction synthesis and can regulate tissue-specific gene expression. With respect to gap junctions: intercellular communication via gap junctions, as measured by dye and electrical coupling, disappears within 12 hrs in primary rat hepatocytes cultured in serum supplemented media or within 24 hrs in cells in a serum free, hormonally defined medium designed for hepatocytes. Glucagon and linoleic acid/BSA were the primary factors in the HDM responsible for the extended life span of the electrical coupling. Addition of proteoglycans or glycosaminoglycans to hormonally defined medium after 24 hrs resulted in reexpression of electrical and dye coupling when assayed at 96 hrs of culture. The incidence of coupling was less than 5% in hormonally defined medium alone. Coupling incidence increased to 10-30% with the addition of 10 micrograms/ml of glycosaminoglycans (i.e., hyaluronic acid, dermatan sulfate, chondroitin 4- or 6-sulfate, and iota- or kappa-carrageenan) to hormonally defined medium. By contrast, the same concentrations of chondroitin sulfate proteoglycan, dermatan sulfate proteoglycan, or lambda-carrageenan resulted in dye coupling in more than 70% of the cells, with numerous cells showing dye spread from a single injected cell (in the case of the proteoglycans). The greatest effect of those tested was elicited by the dermatan sulfate proteoglycans, which induced cell-cell communication in 90-100% of the cells. Heparins gave intermediate responses (30-50%). Western blots demonstrated that the amounts of the main intrinsic gap junction polypeptide (27 KDa) extractable from cells correlated with the degree of electrical and dye coupling. Thus, proteoglycans and glycosaminoglycans appear to elicit the formation and function of gap junctions and may thus play a role in the regulation of intercellular communication under normal and pathological conditions. With respect to gene expression: normal rat hepatocytes maintained in culture on tissue culture plastic and in serum supplemented medium lose their tissue-specific functions within hours to a few days due to loss of synthesis and to rapid degradation of tissue-specific mRNAs.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1985

Nuclear magnetic resonance spectroscopy of rat ventricles following chronic hypoxia: a model of right ventricular hypertrophy.

Nuclear magnetic resonance spectroscopy was used to study the effect of chronic hypoxia on both right (RV) and left ventricular and septal (LV + S) muscle. Rats in the hypoxic group, kept in a hypobaric chamber at 1/2 atm pressure for 2 weeks, developed right, but not left, ventricular hypertrophy (p less than 0.001). Tissues were studied within 2.5 h of return to air. T1 and T2 relaxation times of RV, LV + S and thigh muscle (Th) from hypoxic and control rats were compared. The T2 value distinguished hypoxic from control RV (p less than 0.002), but not hypoxic from control LV + S or Th, indicating that the change in relaxation time reflects cellular hypertrophy, and not hypoxemia. For hypoxic rats only the T2 value distinguished each muscle type: RV from LV + S (p less than 0.009), RV from Th (p less than 0.001) and LV + S from Th (p less than 0001). The T1 value did not identify either the hypoxic or control group or the type of muscle. Percent water content was similar for all tissues. For hypoxic RV, T2 correlated with the percent water content (r = 0.89; p less than 0.01). The sensitivity of T2 to the cellular changes associated with hypoxic RV hypertrophy could provide a means of detecting right ventricular hypertrophy.

Animals↗
PubMed1985

Correction of congenital diaphragmatic hernia in utero. IV. An early gestational fetal lamb model for pulmonary vascular morphometric analysis.

Infants born with congenital diaphragmatic hernia (CDH) often have specific pathologic abnormalities of the pulmonary microcirculation that result in high pulmonary vascular resistance and extrapulmonary right-to-left shunting after birth. In an attempt to make an animal model with similar vascular changes, we created CDH in fetal lambs at 60 to 63 days gestation, repaired some at 100 to 113 days gestation, and subsequently performed morphometric analysis of the pulmonary vasculature. Creation of CDH at this early gestational age resulted in a high fetal mortality rate. In the unrepaired CDH lambs, the pulmonary vascular abnormalities were more severe in the left lung. Similar to human CDH, diaphragmatic hernia in the fetal lamb resulted in a decrease in the total size of the pulmonary vascular bed, a decrease in the number of vessels per unit area lung, and increased muscularization of the arterial tree. Fetal surgical repair of CDH restored the pulmonary arterial bed towards normal.

Animals↗
PubMed1985

Congenital diaphragmatic hernia: arterial structural changes and persistent pulmonary hypertension after surgical repair.

Some infants with congenital diaphragmatic hernia who die after surgical correction have a transient postoperative period during which systemic oxygenation is adequate (honeymoon period), whereas others have persistent hypoxemia. Using morphometric techniques, we analyzed lung structure, especially the arterial bed, in seven infants who died within 1 week of surgical repair. Three infants comprised the honeymoon group, the PaO2 transiently being greater than 150 mm Hg in the descending aorta (FiO2 1.0); four infants comprised the no-honeymoon group and never had PaO2 greater than 85 mm Hg. All lungs were hypoplastic for age; with one exception, infants in the no-honeymoon group had smaller lungs. Arterial structure in the no-honeymoon group contributed to a greater reduction in pulmonary arterial cross-sectional area. Each infant in the no-honeymoon group had muscularization of intra-acinar arteries and failure of perinatal increase in compliance of small preacinar arteries, features not seen in the honeymoon group or in the normal newborn infant. In addition, compared with the honeymoon group, luminal area of preacinar and intra-acinar arteries in the no-honeymoon group was decreased by reduced external diameter or increased medial thickness. Clinical deterioration in the honeymoon group is based on a vasoconstrictive response of the hypoplastic vascular bed. Persistent hypoxemia in the no-honeymoon group is based on both severity of pulmonary hypoplasia and structural remodeling of the pulmonary arteries.

Arteries↗
PubMed1985

Effect of vasodilators at rest and during exercise in young adults with cystic fibrosis and chronic cor pulmonale.

Six clinically stable patients with cystic fibrosis (24 to 31 yr of age) and severe pulmonary impairment, right ventricular hypertrophy, and previous right-sided heart failure underwent cardiac catheterization to assess the hemodynamic effects of oxygen (fraction of inspired O2, 0.31, 0.50), phentolamine (5 mg intravenously), hydralazine (0.33 mg/kg intravenously), and nifedipine (20 mg sublingually). Measurements during dynamic exercise were also obtained before and after hydralazine therapy. Studies after 5 to 8 wk of continuous, orally administered hydralazine therapy were performed in 3 patients. The resting mean pulmonary artery pressure was 31 +/- 4 mmHg. At rest, only oxygen was a selective pulmonary vasodilator, decreasing pulmonary artery pressure and pulmonary vascular resistance in all patients. Systemic arterial pressure and resistance were not significantly changed. Phentolamine, hydralazine, and nifedipine did not alter pulmonary artery pressure or selectively affect the pulmonary vascular bed, reducing both calculated pulmonary and systemic vascular resistance, the latter to a similar or greater degree. Hydralazine and nifedipine significantly increased cardiac index and decreased systemic arterial pressure. Nifedipine mildly decreased systemic oxygenation. During exercise, the mean pulmonary artery pressure increased to 51 +/- 15 mmHg. Hydralazine increased systemic and mixed venous oxygenation both at rest and during exercise but did not alter the elevation in pulmonary artery pressure observed during exercise. After orally administered hydralazine therapy, oxygen delivery and cardiac index remained increased in 2 patients. These data support the use of oxygen but not of the other agents in patients with cystic fibrosis and chronic cor pulmonale unless the ability of hydralazine to increase oxygen delivery is determined to improve prognosis.

Adult↗
PubMed1985

Density gradient study of bronchial mucus aspirates from healthy volunteers (smokers and nonsmokers) and from patients with tracheostomy.

Because it is difficult to obtain, little is known of bronchial mucus from the normal human airway; it has been mainly studied as sputum expectorated in chronic bronchitis with particular attention to epithelial glycoprotein. We have now applied density gradient methods to study this and other macromolecules and lipids in normal airway mucus. After lavage at bronchoscopy, mucus was aspirated from six normal volunteers, that include one light and two heavy smokers. This normal mucus has been compared with that obtained from four patients with tracheostomy because of respiratory muscle paralysis due to neurological disease. The normal aspirates contained small threads of mucus, the tracheostomy aspirates viscous blobs of jelly, a difference in physical appearance reflected in macromolecular yields, 0.3-1 mg/ml and 6-24 mg/ml respectively. On analytical ultracentrifugation normal mucus showed no discernible material in the buoyant density region typical of epithelial glycoprotein (1.5 g/ml): Virtually all the material migrated to the miniscus and was predominantly lipids and proteins. A trace amount of material recovered from a higher density region (greater than or equal to 1.6 g/ml) was found to contain both glycoprotein and proteoglycan. Aspirates from the heavy smokers contained appreciable amounts of material with typical buoyant density (approximately 1.5 g/ml) but still with features of proteoglycan. In contrast in tracheostomy aspirates epithelial glycoprotein of typical buoyant density and chemical composition accounted for up to 25% of nondialyzable material. We conclude that under normal conditions typical epithelial glycoprotein is virtually absent from airway mucus and that the glycoconjugate present has features of glycoprotein and proteoglycan.

Adult↗
PubMed1985

Effect of methylprednisolone on monocrotaline-induced pulmonary vascular disease and right ventricular hypertrophy.

Methylprednisolone (MP) has been shown to reduce acute lung edema caused by monocrotaline (MCT), but its effect on MCT-induced pulmonary hypertension has not previously been reported. We have examined the effects of MP on MCT-induced pulmonary vascular remodeling and right ventricular hypertrophy using five groups of rats. Group 1 received nothing and acted as control; group 2 and all other groups received MCT as a single injection; group 3 was given low-dose MP by daily injection starting 24 hours after the MCT; group 4 was given MP as two high-dose pulses 2 hours before and 22 hours after MCT; group 5, acting as control for injection, received an injection of water 2 hours before MCT and daily for 21 days. All animals were killed 21 days after the MCT was given; ventricular weights were determined, and the lung vasculature was analyzed morphometrically. In each of the last three groups, the "treatment" reduced the increase in arterial medial thickness, "extension" of muscle to intraacinar pulmonary arteries, number of vessels with "occluded" lumen, and right ventricular hypertrophy--the features caused by MCT alone. For all four features, the effectiveness of a given regimen was similar. Daily MP prevented three-quarters of the ventricular ratio change, whereas pulse MP and daily water prevented one-half. The protection given by daily water injection may relate to autologous hormone production (steroid or other) from stress of injections. Daily MP, given after the acute MCT injury has occurred, protects more effectively than a high-dose pulse given at the time of injury. We suggest that the acute phase of MCT injury causes secondary changes that, although triggered by the acute lesion, become self-sustaining and are more significant for vascular structural remodeling.

Animals↗
PubMed1985

The effect of isoproterenol on the development and recovery of hypoxic pulmonary hypertension. A structural and hemodynamic study.

Isoproterenol, administered intravenously during acute hypoxic exposure, is here shown to prevent about two-thirds of the rise in pulmonary artery pressure in unanesthetized male Sprague-Dawley rats with normal pulmonary vascular beds. In rats receiving continuous intravenous infusion of isoproterenol during 2 weeks' exposure to chronic hypobaric hypoxia (FiO2 0.1) the drug does not prevent either the hemodynamic or pulmonary structural changes caused by hypoxia. Similar drug administration to rats in air causes a mild increase in pulmonary artery muscularity including extension and hypertrophy of both the left and right ventricles, without changing hemodynamic findings. Isoproterenol administered during 2 weeks' recovery in air after 2 weeks' hypoxia not only prevents the usual structural recovery, but several structural features actually progress. In contrast, it does not prevent hemodynamic recovery, perhaps because the hematocrit is lower in the isoproterenol-treated rats than in rats recovering without isoproterenol. Administered in air to rats with pulmonary vascular beds remodeled by chronic hypoxia, it does not reduce pulmonary artery pressure.

Animals↗
PubMed1984

Airway mucus: composition and regulation of its secretion by neuropeptides in vitro.

Human and canine airway mucosa in vitro synthesizes and secretes mucus glycoprotein, proteoglycans and lipids which can be separated by density gradient ultracentrifugation in caesium bromide. In secretions from unstimulated explants, the small amount of mucus glycoprotein present is found in association with proteoglycans. 'Free' mucus glycoprotein of typical buoyant density is present only after stimulation of submucosal gland secretion by methacholine. Lipids are synthesized, at least in part, by the airway mucosa and occur in explant secretions as a viscoelastic gel, suggesting that they significantly influence the rheological properties of airway mucus. In addition to cholinergic and adrenergic secretomotor neurons, the airway mucosa is innervated by peptidergic fibres containing immunoreactivity to vasoactive intestinal peptide (VIP) and substance P (SP). In explants of non-bronchitic human airway, VIP inhibits baseline glycoprotein and lysozyme secretion; in canine airway mucosa, by contrast, VIP is a weak partial secretory agonist. SP is the most potent agonist of canine airway glycoprotein release described to date and appears to evoke secretion by a direct action on a stereospecific SP receptor rather than by inducing release of other endogenous secretagogues. VIP and SP have little effect on glycoprotein discharge by mucous and serous cells of the submucosal gland; SP appears to induce secretion by causing contraction of submucosal gland ducts. This may represent the most rapid way for delivering mucus into the airway in response to injury or irritation of airway epithelium.

Animals↗
PubMed1984

Laminin as a substrate for retinal axons in vitro.

Fetal mouse retinal ganglion cell axons have been shown to ramify within co-cultured basement membrane secreting tumor explants and upon isolated basement membranes. Here we report that laminin, a glycoprotein found in basement membranes and adhesion sites of a variety of cell types, acted as a substrate for retinal explant attachment and axonal outgrowth. When axons were given a direct choice, laminin was preferred over collagen. Under suitable conditions (air-dried upon underlying collagen gels), laminin was more effective than fibronectin for promoting axon emergence from retinal explants. These findings have implications for the study of molecular mechanisms underlying CNS axonal outgrowth.

Animals↗
PubMed1984

Pulmonary vascular disease in fatal meconium aspiration.

Although not proved, it is generally accepted that pulmonary vasospasm is responsible for the persistent pulmonary hypertension frequently associated with meconium aspiration. We have studied the pulmonary vasculature in 11 consecutive infants with fatal meconium aspiration, applying morphometric techniques to pulmonary arteries distended with barium gelatin before fixation. In 10 of the 11 infants, persistent pulmonary hypertension was evident clinically, with right-to-left shunting through the foramen ovale or ductus arteriosus. In all but one, severe structural abnormal muscularization of the smallest intra-acinar arteries was present. These changes must have developed before birth. In only one infant was the structure of the intra-acinar precapillary arteries virtually normal, as would be expected if vasospasm alone had caused the hypertension. The persistent pulmonary hypertension associated with fatal meconium aspiration may be the result of a structurally abnormal pulmonary microcirculation.

Female↗