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Biomedical subjects

R A Berg

Publications and source records attributed to R A Berg.

At least 19 recordsLinked to original sources
PubMed1992

Collagenase expression in the lungs of transgenic mice causes pulmonary emphysema.

Transgenic mice were generated that expressed a human collagenase transgene in their lungs under the direction of the haptoglobin promoter. Histological analysis demonstrated disruption of the alveolar walls and coalescence of the alveolar spaces with no evidence of fibrosis or inflammation. This pathology is strikingly similar to the morphological changes observed in human emphysema and therefore implicates interstitial collagenase as a possible etiological agent in the disease process. Although elastase has been proposed as the primary enzyme responsible for emphysematous lung damage, this study provides evidence that other extracellular matrix proteases could play a role in emphysema. In addition, these transgenic mice are a defined genetic animal model system to study the pathogenesis of emphysema.

Animals↗
PubMed1992

Dobutamine stress echocardiography: a sensitive indicator of diminished myocardial function in asymptomatic doxorubicin-treated long-term survivors of childhood cancer.

Doxorubicin is an effective anticancer chemotherapeutic agent known to cause acute and chronic cardiomyopathy. To develop a more sensitive echocardiographic screening test for cardiac damage due to doxorubicin, a cohort study was performed using dobutamine infusion to differentiate asymptomatic long-term survivors of childhood cancer treated with doxorubicin from healthy control subjects. Echocardiographic data from the experimental group of 21 patients (mean age 16 +/- 5 years) treated from 1.6 to 14.3 years (median 5.3) before this study with 27 to 532 mg/m2 of doxorubicin (mean 196) were compared with echocardiographic data from 12 normal age-matched control subjects. Graded dobutamine infusions of 0.5, 2.5, 5 and 10 micrograms/kg per min were administered. Echocardiographic Doppler studies were performed before infusion and after 15 min of infusion at each rate. Dobutamine infusion at 10 micrograms/kg per min was discontinued after six studies secondary to a 50% incidence rate of adverse symptoms. The most important findings were that compared with values in control subjects, end-systolic left ventricular posterior wall dimension and percent of left ventricular posterior wall thickening in doxorubicin-treated patients were decreased at baseline study and these findings were more clearly delineated with dobutamine stimulation. End-systolic left ventricular posterior wall dimension at baseline for the doxorubicin-treated group was 11 +/- 1.9 mm versus 13.1 +/- 1.5 mm for control subjects (p less than 0.01). End-systolic left ventricular posterior wall dimension at the 5-micrograms/kg per min dobutamine infusion for the doxorubicin-treated group was 14.1 +/- 2.4 mm versus 19.3 +/- 2.6 mm for control subjects (p less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1992

Accuracy of central venous pressure monitoring in the intraabdominal inferior vena cava: a canine study.

STUDY OBJECTIVE: To test the hypotheses that in multiple pathophysiologic settings (1) end-expiratory central venous pressure measurements in the intraabdominal inferior vena cava accurately reflect those in the superior vena cava and (2) mean central venous pressure monitoring is as reliable in the inferior vena cava as it is in the superior vena cava. DESIGN: Simultaneous inferior vena caval and superior vena caval pressures were measured during five ventilatory phases: apnea, end-expiratory mechanical ventilation, maximal inspiratory mechanical ventilation, end-expiratory spontaneous ventilation, and maximal inspiratory spontaneous ventilation. Measurements were repeated after progressive intravascular volume depletion. SUBJECTS: Eight puppies. MEASUREMENTS AND RESULTS: Simultaneous inferior vena caval and superior vena caval end-expiratory pressures did not differ significantly (mean differences 0 to 0.1 mm Hg) and the limits of agreement of these measurements were within 2 mm Hg. Differences between mean maximal inspiratory pressures in the inferior vena cava and superior vena cava during mechanical and spontaneous ventilation were -0.7 and 3.6 mm Hg, respectively (p less than 0.01), and the limits of agreement extended beyond 2 mm Hg. Furthermore, mean maximal inspiratory pressures in the superior vena cava differed from end-expiratory pressures in the superior vena cava (1.1 and -3.6 mm Hg, p less than 0.01), whereas those in the inferior vena cava did not differ from end-expiratory superior vena caval pressures. CONCLUSIONS: Under the experimental conditions studied (1) end-expiratory intraabdominal inferior vena caval pressures accurately reflected end-expiratory superior vena caval pressures and (2) mean central venous pressure monitoring was as reliable in the inferior vena cava as in the superior vena cava.

Abdomen↗
PubMed1992

Neuropsychological performance and suicidal behavior in adult psychiatric inpatients.

Although various studies have shown that suicidal persons exhibit greater cognitive deficiencies than both normals and other psychiatric patients, researchers as yet have been unable to account for the source(s) of the differences. Some of these differences (e.g., cognitive rigidity and impaired problem solving) hint of possible organic involvement. This study explored the relationship of neuropsychological functioning to suicidal behavior by comparing 20 suicidal and 27 nonsuicidal psychiatric inpatients on several tests of neuropsychological functioning. Although results showed no significant differences between the two groups on most measures, both groups showed evidence of notably high levels of cortical dysfunction relative to test norms. Thirty-five percent of suicidal patients and 44% of nonsuicidal patients scored in the impaired range. Implications of this high frequency of impairment for the treatment of suicidal and nonsuicidal psychiatric patients are discussed.

Adult↗
PubMed1992

Accuracy of central venous pressure measurement from the abdominal inferior vena cava.

Central venous pressure measurements in the abdominal inferior vena cava were compared with measurements in the right atrium in 10 infants and 10 children during cardiac catheterization. At end expiration, the mean pressures at these two sites were within 1 mm Hg of each other in all 20 patients, with a mean difference of 0.0 +/- 0.36 mm Hg. The abdominal inferior vena cava is a safe and convenient site for measurement of central venous pressure, and our study confirms that such measurements are accurate.

Adolescent↗
PubMed1991

A novel 53-kDa polypeptide from chicken embryo.

We have isolated from chicken embryos a novel 53-kDa protein possessing properties which are similar, but not identical to the 55-kDa PDI polypeptide from chicken embryos. The novel 53-kDa polypeptide copurifies with PDI, but is separated by ion-exchange chromatography. The novel 53-kDa polypeptide cross-reacts strongly with antibodies specific for bovine PDI and cross-reacts to varying degrees with six different preparations of antibodies specific for chicken PDI which is identical to the beta-subunit of chicken prolyl 4-hydroxylase. Anti-bovine PDI immunoglobulins selected by the purified 53-kDa polypeptide react with bovine PDI but not with the beta-subunit of prolyl 4-hydroxylase, suggesting that the 53-kDa polypeptide shares epitopes with bovine PDI but not with the chicken prolyl 4-hydroxylase beta-subunit. Amino acid compositional analysis of the purified polypeptide yielded unique data when compared to PDI and other PDI-like polypeptides. Edman degradation from the N terminus of the 53-kDa polypeptide yields a sequence very different from the N terminus of PDI. This sequence is unique when compared to all entries in available databases. A 20-residue sequence of an internal cyanogen bromide fragment of the 53-kDa polypeptide gives a nearly identical match with human beta-endorphin. The 53-kDa polypeptide is capable of cleaving the disulphides of insulin under conditions where PDI is active. The periodic acid-Schiff assay failed to detect bound carbohydrate. These observations support evidence for a family of PDI-like proteins in chicken embryo and suggest that PDI activity is not confined to only one protein.

Amino Acid Sequence↗
PubMed1991

Modulation of collagen synthesis by growth factors: the role of ascorbate-stimulated lipid peroxidation.

Ascorbic acid has been shown to stimulate collagen synthesis through induction of lipid peroxidation leading to increased transcription of the collagen genes. The mechanism by which lipid peroxidation stimulates collagen transcription is unknown; however, an alteration of cell membranes may affect the activity of serum growth factors leading to a change in gene expression. To test this hypothesis, we treated dermal fibroblasts with transforming growth factor-beta (TGF-beta), epidermal growth factor (EGF), interleukin-1 (IL-1), platelet-derived growth factor (PDGF), or fibroblast growth factor (FGF) in the presence of lipid peroxidation stimulating (200 microM) and nonstimulating (1 microM) concentrations of ascorbic acid. EGF and IL-1 had no effect on collagen synthesis at either concentration of ascorbic acid. FGF affected collagen synthesis only in the presence of 200 microM ascorbic acid, producing both a stimulation (0.4-2 ng/ml) and an inhibition (greater than 50 ng/ml). PDGF and TGF-beta stimulated collagen synthesis in the presence of both concentrations of ascorbic acid, with TGF-beta producing an 11-fold increase in collagen synthesis in the presence of ascorbate. This synergism produced by the combination of ascorbic acid and TGF-beta was inhibitable by the lipid peroxidation inhibitor, propyl gallate. These results indicate that regulation of collagen synthesis by ascorbic acid does not occur through altering the response to EGF or Il-1. Ascorbate has no effect on PDGF but the effects of TGF-beta and FGF on collagen synthesis appear to be sensitive to lipid peroxidation.

Ascorbic Acid↗
PubMed1991

Correlation of the steady-state RNA levels among the alpha-subunit of prolyl 4-hydroxylase and the alpha 1 and alpha 2 chains of type I collagen during growth of chicken embryo tendon fibroblasts.

The relative steady-state levels of RNAs encoding type I collagen and prolyl 4-hydroxylase were examined in exponentially growing primary cultures of chicken embryo tendon fibroblasts. The RNA levels of the alpha 1 and alpha 2 chains of type I collagen were maximal when the fibroblasts reached the confluent state. The RNA levels of the alpha-subunit of prolyl 4-hydroxylase were also maximal at confluency and rose and fell with the RNA levels of the two collagen chains. The RNA levels of the beta-subunit of prolyl 4-hydroxylase did not correlate with the changes observed for the alpha-subunit or for either chain of type I collagen. The RNA levels of the beta-subunit were slightly higher than the RNA levels of the alpha-subunit. These results support our hypothesis that the synthesis of the alpha-subunit and thus the association of newly synthesized alpha-subunits with pre-existing beta-subunits is the rate-limiting factor in determining prolyl 4-hydroxylase activity in cultured cells.

Animals↗
PubMed1991

Neutrophil collagenase activation: the role of oxidants and cathepsin G.

The events leading to neutrophil collagenase activation in vivo were analyzed using phorbol myristate acetate (PMA) stimulated neutrophil supernatant. Under the conditions when this supernatant was incubated with the serine proteinase inhibitor, phenylmethylsulfonyl fluoride (PMSF), and then treated with the oxidant, hypochlorous acid (HOCl), collagenase was activated. When cathepsin G, a known activator of neutrophil collagenase, was also present, less HOCl was required to activate the latent collagenase. These experiments support the conclusion that activation of neutrophil collagenase occurs in vivo by both an oxidant and an enzymatic mechanism where the effectiveness of oxidants is enhanced by cathepsin G.

Cathepsin G↗
PubMed1991

Regulation of collagen synthesis by ascorbic acid: characterization of the role of ascorbate-stimulated lipid peroxidation.

Recently, we have described the ability of traditional lipid peroxidation inhibitors to inhibit ascorbate-stimulated collagen synthesis. In order to characterize further this effect, we have tested the ability of known and potential inhibitors of lipid peroxidation for their effects on ascorbate-stimulated collagen synthesis and lipid peroxidation. In our experiments, mannitol, a water soluble antioxidant, had no effect on ascorbate-induced collagen synthesis nor on lipid peroxidation. However, alpha-tocopherol, which is a lipophilic antioxidant, inhibited both effects of ascorbate. Superoxide dismutase, catalase, and their polyethylene glycol conjugate forms did not inhibit the ascorbate-stimulated collagen synthesis or lipid peroxidation. In addition, no effect was seen with the oxygen radical scavengers isopropanol, ethanol, or dimethyl sulfoxide. Two iron chelators, o-phenanthroline and alpha,alpha-dipyridyl, both inhibited ascorbate-induced lipid peroxidation and collagen synthesis, consistent with the previously described iron-dependence of lipid peroxidation by ascorbate. These results support a correlation between collagen synthesis and lipid peroxidation and provide a theory for the mechanism of ascorbic acid regulation of collagen synthesis.

Antioxidants↗
PubMed1991

Thermal laser assisted balloon angioplasty in lower extremity occlusive disease.

Results of Nd:Yag thermal laser assisted balloon angioplasty (LABA) in lower extremity occlusive disease were reviewed retrospectively in 23 patients and 28 lesions over a 1 year period. Indications for intervention were progressive claudication in 74 per cent and gangrene and/or rest pain in 26 per cent. Twenty-four (86%) procedures were technically successful; however, there were only 15 (54%) clinical successes during the follow-up period (0.5-12.5 months). Complications occurred following ten (36%) procedures with one mortality (4%) unrelated to the procedure. Analysis of the nature and location of the lesions revealed five angiographic patterns with varying degrees of success. These are: Superficial Femoral and Popliteal: 1) short segment stenosis--2/3, 2) long multisegment stenosis--1/6, 3) total occlusion--7/9, 4) stenosis and occlusion--2/4; Iliac: 5) stenosis--3/4. The only subsets of patients who appeared to benefit from LABA were those with short segment stenosis or isolated occlusions. Patients with good runoff also did well. Patients with poor runoff or multiple stenoses associated with diffuse disease did poorly. It is concluded that LABA has limited applications in the treatment of lower extremity occlusive disease.

Adult↗
PubMed1991

Activities of a cancellous bone-cell-stimulating substance.

A bone-cell-stimulating substance (BCSS) that initiates appositional bone formation in intact rats was examined for its effects on DNA and collagen synthesis in tibial and calvarial organ cultures of 17-day-old embryonic chicks. BCSS stimulated collagen synthesis in both types of bone. BCSS stimulated DNA synthesis in tibiae but inhibited synthesis in calvaria from the same chicks. Insulinlike growth factor, transforming growth factor-beta, platelet-derived growth factor, and fetal bovine serum also affected DNA synthesis differently in calvaria and tibiae. BCSS was able to modify some of the effects of these growth factors on DNA.

Animals↗
PubMed1990

Retinoids affect collagen synthesis through inhibition of ascorbate-induced lipid peroxidation in cultured human dermal fibroblasts.

Ascorbate has been shown to stimulate collagen synthesis in cultured human dermal fibroblasts by increasing transcription of the collagen genes. In the present studies, ascorbate stimulates lipid peroxidation at concentrations similar to those necessary to affect collagen synthesis. Molecules which inhibit lipid peroxidation, such as propyl gallate, cobalt chloride, and alpha-naphthol, also inhibit collagen synthesis, suggesting a correlation between the two phenomena. Retinoic acid and some synthetic retinoids have previously been shown to inhibit collagen synthesis in cultured human dermal fibroblasts. In our studies two different retinoids, at similar concentrations, inhibit both ascorbate-stimulated lipid peroxidation and collagen synthesis. Since high concentrations of retinoids were required, the ability of retinoids to inhibit the oxidant effect of ascorbate, and not their receptor-mediated activity, may be responsible for their effect on collagen synthesis.

Antioxidants↗
PubMed1990

Protein disulphide isomerase from human peripheral blood neutrophils.

Protein disulphide isomerase (PDI) is a 56 kDa resident polypeptide of the endoplasmic reticulum of many cell types. We evaluated the ability of human peripheral blood polymorphonuclear neutrophils (PMN) to synthesize both mRNA and proteins. Using in vitro [35S]-methionine labeling of purified PMN, followed by immunoprecipitation of cell lysates with immobilized polyclonal and monoclonal antibodies and analysis by gel electrophoresis, PMN were shown to synthesize many proteins, including actin. In contrast, incorporation of [35S]-methionine into PDI was not detected. Purification of total RNA from PMN and analysis by Northern blots demonstrated the presence in PMN of PDI-RNA. Western immunoblot evaluations of total PMN protein display an immunoreactive-PDI of 56 kDa. Indirect immunofluorescence studies suggest an abundance of immunoreactive-PDI throughout PMN. We therefore conclude that PDI is synthesized in precursor cells of the bone marrow. Phorbol 12-myristate 13-acetate, a reagent known to affect the degranulation of specific granules, causes the release of immunoreactive-PDI into a post-centrifugation supernatant. PDI, a ubiquitous endoplasmic reticulum resident protein, is shown here to be associated with specific granules in a cell type which has lost its intracellular membrane network during terminal differentiation.

Animals↗
PubMed1990

Mechanical stress and cellular metabolism in living soft tissue composites.

A soft tissue substitute composed of a three-dimensional collagen lattice infiltrated with living fibroblasts was modelled as a two-phase composite material. The phases consisted of an extracellular matrix containing fibres and fluid and cellular inclusions. A mathematical model that had been previously derived for calculating the elastic stress and energy distribution around spherical inclusions and voids in a three-dimensional elastic medium was applied to a biological composite containing cells in an elastic medium. The model predicted an increase in stress inside the cells in the direction of applied load and a decrease in the direction perpendicular to the applied load. The model also predicted increased interfacial stress at the cell-matrix boundary in the direction of applied load with maximum and minimum values at different points on the cell periphery. It was hypothesized that the interfacial stress around the cell inclusions might play a function in signal transduction. To test this hypothesis, an average unidirectional stress was applied to the boundary of a 1 cm X 2 cm X 3 mm lattice containing fibroblasts. When cells were cultured for 7 d and placed under stress of 15 g, cell growth was increased 1.7 fold, protein synthesis decreased 48% and intracellular cAMP was increased 3.7 fold in 24 h. The changes were a function of externally applied stress. Cells cultured for 14 d and placed under stress displayed similar results. The results supported the concept that soft tissue extracellular matrix depicted as an elastic medium can affect cell growth and development.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗