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Biomedical subjects

A Warner

Publications and source records attributed to A Warner.

At least 19 recordsLinked to original sources
PubMed1992

Gap junctions in development--a perspective.

The status of the gap junction as a pathway for cellular interactions during development is reviewed. Current evidence suggests that gap junctions play an important part in ensuring normal development, although the precise role of gap junctional communication remains to be defined. Communication through gap junctions acts alongside cellular interactions achieved by the release of growth factors during embryogenesis. Differences between groups of developing cells may be reflected in, and possibly controlled by, alterations in the selectivity of the gap junctions. It seems likely that gap junctional communication is involved in the control of embryonic patterning rather than phenotypic differentiation.

Animals↗
PubMed1992

The relationship of gap junctions and compaction in the preimplantation mouse embryo.

In the mouse embryo, gap junctions first appear at the 8-cell stage as compaction is about to take place. Compaction of the embryo is important for the differentiation of the first two cell types; the inner cell mass and the trophectoderm. Our studies examine the contribution of gap junctional communication at this stage of development. We have characterised the normal sequence of appearance of gap junction protein and its distribution. The extent of communication as shown by the passage of dye between cells has been recorded in both normal embryos and embryos treated with drugs that influence gap junctional communication. Comparisons have been made with embryos that express a lethal gap junction defect and attempts were made to rescue such embryos by increasing their gap junction communication.

Animals↗
PubMed1991

Effects of captopril on contractility after myocardial infarction: experimental observations.

After large myocardial infarction, compromised left ventricular (LV) function and changes in the peripheral circulation result in the syndrome of chronic congestive heart failure. Although treatment with angiotensin-converting enzyme inhibitors improve cardiovascular function, it is difficult to determine whether this benefit is due to changes in organ versus muscle function. The rat model of heart failure, created by ligating the left coronary artery, results in pathophysiology that is similar to that seen in patients, i.e., increased LV end-diastolic pressure and volume, hypertrophy of the noninfarcted myocardium, prolongation of the time constant of LV relaxation, decreased venous compliance, and increased total blood volume. In noninfarcted papillary muscles, isolated from rats with heart failure, maximal developed tension and peak rate of tension rise (+dT/dt) are decreased, time to peak tension is prolonged, and myocardial stiffness is increased. Morphologic changes include an increase in papillary muscle myocyte cross-sectional area and an increase in myocardial hydroxyproline content. Captopril (2 g/liter drinking water) alters LV loading by decreasing arterial pressure, increasing venous compliance, and decreasing blood volume. This results in a decrease in LV end-diastolic pressure and volume. In the noninfarcted myocardium, time to peak tension is shortened, whereas developed tension, +dT/dt, and muscle stiffness remain abnormal. Captopril decreases myocyte cross-sectional area, but collagen content remains elevated. Thus, in the rat infarct model of heart failure, treatment with captopril alters LV remodeling and hypertrophy but produces only modest improvement in muscle function.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Uptake of Pneumocystis carinii mediated by the macrophage mannose receptor.

Human exposure to Pneumocystis carinii is common but, in the absence of acquired or genetic dysfunction of either cellular or humoral immunity, exposure rarely leads to illness. Although alveolar macrophages can degrade P. carinii, macrophage receptors involved in P. carinii recognition have not been clearly defined. Characterization of a predominant surface glycoprotein of the high mannose type led us to investigate the role of the macrophage mannose receptor in this process. We report here that binding and uptake of cultured rat P. carinii by human and rat alveolar macrophages is reduced by 90% in the presence of competitive inhibitors of mannose receptor activity and by adherence of alveolar macrophages to mannan-coated surfaces. Further, only those COS cells transfected with the human macrophage mannose receptor complementary DNA that express surface mannose receptors bind and ingest P. carinii. These studies establish that the macrophage mannose receptor is sufficient for uptake of P. carinii and emphasize the role of the alveolar macrophage in first-line host defence against P. carinii.

Animals↗
PubMed1991

Characterization of the airway smooth muscle muscarinic receptor in vivo.

We examined the bronchodilator activity of eight subtype-selective and non-selective muscarinic antagonists in anesthetized, ventilated guinea pigs bronchoconstricted by carbachol aerosols. Relative bronchodilator potencies were consistent with M3 receptor antagonism and correlated with inhibition of bladder smooth muscle contraction in vivo. We conclude that the airway smooth muscle muscarinic receptor can be functionally characterized in vivo as M3 and that it is of the same subtype as the muscarinic receptor in bladder smooth muscle.

Aerosols↗
PubMed1991

Gap junctional communication during neuromuscular junction formation.

We have tested whether gap junctions form between nerve and muscle during their initial contact, before establishing the chemical synapse. Embryonic Xenopus stage 18-20 myotomes and neural tubes were permeabilized with DMSO to load appropriate reagents, dissociated, and cocultured. When myotomes, loaded with Lucifer yellow, were cocultured with unlabeled neural tube cells, 23% of the neurons contained dye after 24 hr. Affinity-purified gap junction antibodies loaded into myocytes or neurons reduced neuronal labeling significantly to 5%. [3H]uridine nucleotide transfer was observed in both directions between myocytes and neurons. Again gap junction antibodies substantially reduced recipient label. In all cases preimmune IgGs did not reduce transfer. When acetylcholine receptor clustering was examined in cultures containing gap junction antibodies, no difference in the number of neuronally induced AChR clusters was observed. This suggests that the cluster-inducing signal between nerve and muscle does not pass through gap junctions.

Animals↗
PubMed1991

In vitro/in vivo evaluation of hydrochlorothiazide in experimental hydrochlorothiazide/triamterene combination tablets in beagle dogs.

The purpose of this study was to compare experimental formulations containing hydrochlorothiazide (CAS 58-93-5)/triamterene (HCT/TRI) in vitro and in vivo to a commercial tablet formulation (standard). The beagle dog was verified as a good model and was used for the in vivo studies. The commercial tablet and the experimental fast release formulation (FR) resulted in 100% release of HCT within 30 min in dissolution tests, whereas, the slow release formulation (SR) released only 54% HCT after 4 h. Relative bioavailability of the FR and SR formulations were 82 and 41%, respectively, compared to the commercial tablet. The experimental results indicate that HCT absorption occurs throughout the small intestine.

Animals↗
PubMed1990

Molecular characterization of the human macrophage mannose receptor: demonstration of multiple carbohydrate recognition-like domains and phagocytosis of yeasts in Cos-1 cells.

The macrophage mannose receptor is an integral membrane protein expressed on the surface of tissue macrophages. After ligation of mannose-rich glycoconjugates or pathogens, the receptor mediates endocytosis and phagocytosis of the bound ligands by macrophages. The cDNA-derived primary structure of the mannose receptor predicts a cysteine-rich NH2-terminal domain, followed by a fibronectin type II region. The remainder of the ectodomain is comprised of eight carbohydrate recognition-like domains, followed by a transmembrane region, and a cytoplasmic tail. Transfection of the mannose receptor cDNA into Cos-I cells is necessary for receptor-mediated endocytosis of mannose-rich glycoconjugate as well as phagocytosis of yeasts. Deletion of the cytoplasmic tail results in a mutant receptor that is able to bind but not ingest the ligated pathogens, suggesting that the signal for phagocytosis is contained in the cytoplasmic tail.

Amino Acid Sequence↗
PubMed1990

Detection of individual fluorescently labeled reovirions in living cells.

Reovirus serotype 1 (Lang) can be conjugated with rhodamine B or fluorescein isothiocyanate in a way that preserves viral infectivity. We have used epifluorescence microscopy to detect individual virions bound to the surface of cells and to follow in real time the early stages of reovirus infection in living cells. Following uptake of the virus into endocytic vesicles, the movement of these vesicles can be observed readily. The vesicle movement is inhibited by nocodazole or colchicine, consistent with previous findings that the movement of intracellular vesicles is often microtubule-based.

Animals↗
PubMed1990

Spontaneous pneumopericardium in an otherwise healthy full-term newborn.

Neonatal pneumopericardium is usually a complication of mechanical ventilation in premature infants with respiratory distress syndrome. We report a full-term neonate who developed pneumopericardium after forceps delivery and mild asphyxia. The child was never ventilated and had no signs of parenchymal lung disease. The pneumopericardium resolved spontaneously. Although drainage of pneumopericardium is usually recommended, this may not always be necessary when there are no signs of cardiac tamponade.

Humans↗
PubMed1990

Recovery of an epitope recognized by a novel monoclonal antibody from airway lavage during experimental induction of chronic bronchitis.

Prolonged exposure of dogs to high concentrations of SO2 gas results in a syndrome with many of the characteristics of human chronic bronchitis, including cough and chronic mucous hypersecretion as well as airway obstruction. We developed and used a novel monoclonal antibody, GB-4B, raised against epithelial glycoprotein isolated from human hypersecretory mucus to probe airway lavage samples from dogs before and during prolonged exposure to SO2 gas. There were relatively low mean titers of the epitope recognized by GB-4B in airway lavage fluid as evidenced by enzyme-linked immunosorbent assay before exposure to SO2 gas. After 25 to 50 wk of SO2 exposure, the dogs showed a significant increase in pulmonary resistance and there was a significant increase in the titer of the epitope in the airway lavage fluid. Using the same antibody immunohistochemical analysis of airway tissues from SO2-exposed dogs revealed patchy staining of the mucous glands and airway secretory cells and dense staining along the airway surface; airway tissue from control dogs and one SO2-exposed dog whose lavage fluid did not contain the epitope showed little or no staining. These data demonstrate that similar mucin epitopes appear in airway lavage fluid under hypersecretory conditions in both animals and humans. The epitope may have utility as a marker of chronic mucous hypersecretion.

Animals↗
PubMed1990

The role of gap junctions in patterning of the chick limb bud.

The role of gap junctional communication during patterning of the chick limb has been investigated. Affinity-purified antibodies raised against rat liver gap junctional proteins were used to block communication between limb mesenchyme cells. Co-injection of the antibodies and Lucifer yellow into mesenchyme cultures demonstrated that communication was inhibited almost immediately. When antibodies were loaded into mesenchyme tissue by DMSO permeabilization, [3H]nucleotide transfer was prevented for at least 16 h. Polarizing region tissue from the posterior limb bud margin causes digit duplications when grafted to the anterior margin. Quail polarizing region cells were loaded with gap junction antibody and grafted into chick wing buds. The antibody had no effect on growth or survival of the grafted cells. As very few polarizing region cells are required to initiate duplications, the number of polarizing region cells in the grafts was reduced by diluting 1:9 with anterior mesenchyme tissue. When either polarizing region or anterior mesenchyme tissue in the graft was loaded separately with antibody, there was little effect on respecification of the digit pattern. However, loading both tissues in the graft caused a significant decrease in duplications. This indicates that a major role of gap junctions in limb patterning may be to enable polarizing region cells to communicate directly with adjacent anterior mesenchyme. A role for gap junctional communication between anterior mesenchyme cells cannot be excluded. The results are discussed in relation to the role of retinoic acid as a putative morphogen.

Animals↗
PubMed1990

Critical care nurses' attitudes toward, concerns about, and knowledge of the acquired immunodeficiency syndrome.

Two samples of critical care nurses (from a secular teaching hospital and a religious-affiliated community hospital, respectively) were compared on their attitudes, concerns, and knowledge regarding the acquired immunodeficiency syndrome (AIDS). Nurses from the teaching hospital had significantly (p = 0.003) more favorable attitudes toward patients with AIDS than did the community hospital nurses. Modal response in each group for perceived risk of acquiring AIDS from patients was 1 chance in 10,000. If given a choice, a sizable percentage in both the teaching (45%) and the community hospital (65%) groups would refuse to care for patients with AIDS. Those indicating preference for refusing showed significantly higher levels of concern and significantly less favorable attitudes than the others. Knowledge about AIDS was high, with means in each group exceeding 14 out of 16 possible points. Implications for nursing practice are discussed.

Acquired Immunodeficiency Syndrome↗
PubMed1989

Interference of common household chemicals in immunoassay methods for drugs of abuse.

I report how some adulterants affect results for drugs of abuse in urine as measured by Roche RIA, Syva emit d.a.u., and Abbott TDx fpia (fluorescence polarization immunoassay) for the following drugs: amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, opiates, and phencyclidine (PCP). Sodium chloride interfered negatively with all of these drugs when assayed by emit and caused a slight decrease in measured benzodiazepine concentration by fpia. Drug concentrations were also decreased by added H2O2 (emit: benzodiazepine), Joy detergent (emit: cannabinoid, benzodiazepines, PCP), NaHCO3 (emit: opiate; fpia: PCP), or NaClO [corrected] (emit, RIA, fpia: amphetamines, opiates, PCP; emit, fpia: cannabinoid; emit: benzodiazepines). False-positive results were caused by H2O2 (fpia: benzodiazepines) and Joy (RIA, fpia: benzodiazepine, cannabinoid; fpia: barbiturate, amphetamine). Sodium bicarbonate causes a suspiciously high pH in the urine, NaClO [corrected] an apparently low pH (using pH paper).

Amphetamines↗
PubMed1989

Liquid-chromatographic monitoring of cytosine arabinoside and its metabolite, uracil arabinoside, in serum.

This is a "high-performance" liquid-chromatographic method for quantifying the antileukemic drug cytosine arabinoside (cytarabine; 1-beta-D-arabinofuranosylcytosine; Ara-C), with a structural analog, 5-methylcytidine, as the internal standard. We used a C18 reversed-phase column and ammonium acetate (0.5 mol/L, pH 6.5) as the mobile phase, monitoring the column effluent at 280 nm. Tetrahydrouridine was present in the sample-collection tubes to inhibit conversion of cytosine arabinoside to uracil arabinoside. The standard curve is linear to 100 mg/L. Analytical recovery is 98%. Coefficients of variation for within-run and between-run imprecision were 2.0% and 4.3% at 20 mg/L and 2.7% and 2.7% at 80 mg/L, respectively. Assay sensitivity was limited by the amount of endogenous material in each patient's serum, making assay of a pre-infusion sample necessary for accurate calculations. In a trial patient population, the assay was shown to have potential for the detection of toxic concentrations in patients receiving high doses of Ara-C.

Aged↗
PubMed1986

Drug use in the neonate: interrelationships of pharmacokinetics, toxicity, and biochemical maturity.

With advances in technology, increasing numbers of premature and very ill neonates are surviving and being referred for treatment to neonatal intensive-care units. A major feature of the treatment they receive is therapy with drugs. However, because of relatively limited information available in the area of neonatal pharmacokinetics, the few drugs that currently can be monitored directly, and the lack of an effective mechanism for measuring the biochemical and functional maturity of the neonate, especially as it relates to drug clearance, therapy of neonates with drugs is certainly more hazardous and possibly less effective than in adult patients. Toxic reactions of neonates to drug therapy can usually be related to the unique pharmacokinetic processes seen in this group, particularly to the maturity of clearance mechanisms. This is the basis for a link between maturity and drug efficacy or toxicity. In this usage, maturity refers to the functional capacity of organs and biochemical pathways. Of particular concern in this regard is kidney function and the activity of drug-metabolizing enzyme systems. Because direct assessment of these functions in the neonate is difficult, other types of maturity markers that can be easily measured and which relate to drug clearance need to be identified. Such markers could serve as a guide to the physician who is planning drug therapy for a neonatal patient. Several studies looking for a gestational age marker have provided some indication that biochemical maturity markers do exist and simply await discovery, thus affording an integration of pharmacokinetics and pathophysiology to achieve a more rational and effective therapeutic approach.

Adult↗