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Biomedical subjects

D Perry

Publications and source records attributed to D Perry.

At least 55 records · Page 3Linked to original sources
PubMed1996

(1S,2R)-D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol as an inhibitor of ceramidase.

In this study, we have examined the cellular and biochemical activities of the ceramide analog (1S,2R)-D-erythro-2-(N-myristoylamino)-1-phenyl-1-propanol (D-erythro-MAPP). Addition of 5 microM D-e-MAPP to HL-60 human promyelocytic leukemia cells resulted in a concentration- and time-dependent growth suppression accompanied by an arrest in the G0/G1 phase of the cell cycle; thus mimicking the action of exogenous ceramides. Its enantiomer L-e-MAPP was without effect. Two lines of evidence suggested that D-e-MAPP may not function as a direct analog of ceramide. First, D-e-MAPP possesses a stereochemical configuration opposite to that of D-erythro-ceramide. Second, D-e-MAPP failed to activate ceramide-activated protein phosphatase in vitro. Therefore, we examined if D-e-MAPP functioned indirectly by modulating endogenous ceramide levels. The addition of D-e-MAPP to cells, but not L-e-MAPP, caused a time- and concentration-dependent elevation in endogenous ceramide levels reaching greater than 3-fold over baseline following 24 h of treatment. Both D-e-MAPP and L-e-MAPP underwent similar uptake by HL-60 cells. D-e-MAPP was poorly metabolized, and remained intact in cells, whereas L-e-MAPP underwent a time- and concentration-dependent metabolism; primarily through N-deacylation. In vitro, L-e-MAPP was metabolized by alkaline ceremidase to an extent similar to that seen with C16-ceramide. D-e-MAPP was not metabolized. Instead, D-e-MAPP inhibited alkaline ceramidase activity in vitro with an IC50 of 1-5 microM. D-e-MAPP did not modulate the activity of other ceramide metabolizing enzymes in vitro or in cells, and it was a poor inhibitor of acid ceramidase (IC50>500 microM). Finally, D-e-MAPP inhibited the metabolism of L-e-MAPP in cells. These studies demonstrate that D-e-MAPP functions as an inhibitor of alkaline ceramidase in vitro and in cells resulting in elevation in endogenous levels of ceramide with the consequent biologic effects of growth suppression and cell cycle arrest. These studies point to an important role for ceramidases in the regulation of endogenous levels of ceramide.

Acid Ceramidase↗
PubMed1996

Group B Streptococcus and preterm premature rupture of membranes: a randomized, double-blind clinical trial of antepartum ampicillin.

OBJECTIVE: Our purpose was to determine whether ampicillin prolongs the latency period after preterm premature rupture of membranes in patients colonized with group B Streptococcus. STUDY DESIGN: Sixty patients presenting at < or = 35 weeks' gestation with preterm premature rupture of membranes were included in the study. Cervical, vaginal, and perianal cultures for group B premature rupture were obtained. The participants then were randomized to receive either ampicillin or placebo intravenously for 24 hours and then orally until hospital discharge or delivery. All patients were treated without the use of tocolytic drugs. The chi(2) test, Fisher exact test, Student t test, and Wilcoxon signed-rank test were used for statistical analysis when appropriate. RESULTS: Fifteen patients had cultures positive for group B Streptococcus. Patients with cultures positive for group B Streptococcus who received ampicillin (n = 8) were more likely not to have been delivered of their infants 48 hours after preterm premature rupture of membranes than patients who received placebo (n = 7), a statistically significant difference (100% vs 43%; p = 0.01; relative risk 2.3; 95% confidence interval 1.2 to 4.5). Seven days after preterm premature rupture of membranes, however, there was no significant difference in percentage of patients with cultures positive for group B Streptococcus who remained undelivered (63% vs 29%; p = 0.19; relative risk, 2.2; 95% confidence interval 0.7 to 7.1). Among patients with cultures negative for group B Streptococcus, there was a trend for patients who received ampicillin to remain undelivered 48 hours after preterm premature rupture of membranes compared with those who received placebo, but the difference was not statistically significant (87% vs 64%; p = 0.07; relative risk, 1.4; 95% confidence interval 1.0 to 1.9). There also was no difference in percentage of patients with cultures negative for group B Streptococcus who remained undelivered 7 days after preterm premature rupture of membranes 39% vs 27%; p = 0.40; relative risk, 1.4; 95% confidence interval 0.61 to 3.3). There were no differences between the treatment and placebo arms of the group B Streptococcus positive and negative cohorts in incidence of cesarean section, chorioamnionitis, postpartum endometritis, or neonatal infectious morbidity. CONCLUSION: Use of antibiotics increases the percentage of patients with cultures positive for group B Streptococcus who remain undelivered 48 hours after preterm premature rupture of membranes. Antibiotic therapy may provide a window of opportunity for maternal treatment with corticosteroids to decrease the risk for neonatal morbidity among these preterm gestations.

Adult↗
PubMed1995

ADP-ribosylation factor functions synergistically with a 50-kDa cytosolic factor in cell-free activation of human neutrophil phospholipase D.

Proteins in both the cytosol and plasma membrane are needed to reconstitute cell-free phospholipase D activity from phagocytes (Olson, S., Bowman, E. P., and Lambeth, J. D. (1991) J. Biol. Chem. 266, 17236-17242); membrane factors include a small GTP-binding protein in the Rho family (Bowman, E., Uhlinger, D. J., and Lambeth, J. D. (1993) J. Biol. Chem. 268, 21509-21512). ADP-ribosylation factor (ARF) was recently implicated as the cytosolic factor, as it activates phospholipase D in HL-60 membranes. Herein, we show that ion exchange chromatography separates ARF from the major phospholipase D-stimulating cytosolic factor. Both bovine brain ARF and recombinant human ARF-1 stimulated a small amount of phospholipase D activity in the absence of cytosol (about 10% of the response seen with cytosol). With a high concentration of ARF-depleted cytosol, ARF did not further activate. However, at low cytosol, ARF caused marked activation. Thus, ARF synergizes with the cytosolic factor in phospholipase D activation.

ADP-Ribosylation Factors↗
PubMed1995

A property level analysis of lexical semantic representation in Alzheimer's disease.

In order to assess the hypotheses that Alzheimer's disease (AD) results in a property level restructuring, loss, or degradation of lexical-semantic knowledge, Alzheimer's patients and normal elderly subjects were presented with a property verification task in which they were asked to judge the truth value of telegraphic statements which paired objects with their properties (e.g., "Apple is red."). Objects with either high- or low-typical exemplars of categories (e.g., "oak" is a high typical exemplar of the category "tree." while "palm" is a less typical item). Properties were varied with respect to normatively determined dominance (e.g, "fins" is a high dominant property of "trout," while "slimy" is a less dominant property) and whether they were distinctive (i.e., served to distinguish between subsets of exemplars within a category) or shared among most or all category members (e.g., "stem" for the category "fruit"). Analyses of accuracy and reaction time data suggested that AD results in neither a loss per se of representation of properties, nor a reorganization of relations between objects' properties. However, results were consistent with a property level degradation of AD patients' object concepts. While there was no evidence for a differential degradation of distinctive vs shared properties, results suggested that AD patients have degraded representations of lower dominant properties and properties of low-typical category exemplars.

Aged↗
PubMed1995

Sustained increase in haemoglobin and RBC following long-term administration of recombinant human erythropoietin to patients with homozygous beta-thalassaemia.

Recombinant human erythropoietin (rHuEPO) was given subcutaneously three times per week in an escalating dose from 500 u/kg to 950 u/kg together with ferrous fumarate 305 mg and folic acid 5 mg/d, to 10 patients from four unrelated Arab families with homozygous beta-thalassaemia. Six splenectomized patients showed a mean (+/- standard error) increase in haemoglobin from 7.1 +/- 0.1 to 9.3 +/- 0.1 g/dl (P = 0.0001), in RBC from 4.0 to 5.0 x 10(12)/l (P = 0.0001) and in nucleated RBC from 32 +/- 7 x 10(10)/l to 82 +/- 6 x 10(10)/l while receiving 750 u/kg three times per week which persisted for 4-11 months. In two patients there was no need for further blood transfusions. In three out of four unsplenectomized patients there were no changes in Hb and RBC despite dose escalation. There were no significant changes in MVC, MCH and reticulocyte count, serum bilirubin, LDH, malonyldialdehyde (MDA) and vitamin E levels. After 13 weeks of rHuEPO there was a mean increase in the percentage of F cells from 31 +/- 10% to 86 +/- 6% (P < 0.003) in three splenectomized patients and in one unsplenectomized patient from 56.4% to 80% without changes in the levels of Hb F. Globin chain synthesis ratios did not change in four responding patients. Mean serum iron and transferrin saturation index did not change, whereas mean serum ferritin increased from 299 +/- 45 micrograms/l to 480 +/- 20 micrograms/l (P < 0.001). In seven responding patients an accelerated linear growth was indicated by positive changes in height standard deviation score for chronological age. Side-effects were minimal throughout the treatment period.

Administration, Cutaneous↗
PubMed1995

Coronary artery bypass grafting in an achondroplastic dwarf.

To our knowledge, coronary bypass for complications of coronary artery disease in achondroplasia has not previously been described. Achondroplasia, in and of itself, is not a contraindication to coronary bypass. Although the anatomic reserve of saphenous vein is less in achondroplastic dwarfs than in people of normal stature, that vessel and the internal mammary artery can be harvested in routine fashion. A 60-year-old woman with several risk factors for coronary artery disease underwent successful bypass surgery, which included the use of both a saphenous vein and the left internal mammary artery.

Achondroplasia↗
PubMed1994

Postoperative intramyocardial abscess caused by mucormycosis.

We report the case of an intramyocardial abscess caused by mucormycosis that arose after cardiac operation. Several causes of immunosuppression in a 71-year-old woman were exacerbated after she underwent coronary revascularization. Before she died of multiple organ system dysfunction, a variety of supraventricular and ventricular arrhythmias, as well as complete heart block, developed, but the cause was not clear until autopsy revealed a large septal myocardial abscess due to mucormycosis.

Abscess↗
PubMed1993

A brain-tumor model utilizing stereotactic implantation of a permanent cannula.

A tumor model involving stereotactically implanted culture-reared tumor cells is presented. Stainless steel cannulas were stereotactically and permanently implanted into the caudate nucleus of 30 rats. The animals were separated into two groups. In Group I, 15 animals received a 10-microliters injection containing 10(6) C6 glioblastoma cells (five rats), 10(6) Walker 256 breast carcinoma cells (five rats), or cell medium (five rats). The coordinates were A(+1.5), L(+3.0), and DV(-5.0). In Group II, the coordinates were changed to A(+1.0), L(+3.0), and DV(-5.0) and the same number of rats received a 1-microliter injection containing 10(5) cells of each tumor in an attempt to produce more focal tumors. Two weeks after implantation, brain sections were stained with cresyl violet and a subset was stained for glial fibrillary acid protein (GFAP). A computerized morphometric analysis system was used to quantify tumor size. In Group I, the mean C6 tumor areas (+/- standard error of the mean) at specific coordinates were (in sq mm): A(+4.7) 0.4 +/- 0.2; A(+3.7) 3.5 +/- 1.1; A(+2.7) 5.7 +/- 1.7; A(+1.7) 9.5 +/- 2.3; A(+0.7) 7.5 +/- 3.2; A(-0.3) 3.7 +/- 2.9; and A(-1.3) 0.3 +/- 0.3. A nearly identical tumor mass and extension into the brain was produced in rats injected with Walker 256 cells. Similar C6 tumor areas were indicated in adjacent sections stained with cresyl violet and GFAP. Tumor was found in the caudate nucleus in all 10 rats, but not in the nucleus accumbens, fornix, or hippocampus. In Group II animals, tumor magnitude and extension into the brain were greatly reduced. The 10(6) cells in the 10-microliters volume was the most reliable tumor load for obtaining uniform tumors in different animals. The similarity of tumor distribution across different animals was indicated by the low variance of tumor area at specific anteroposterior coordinates. Reproducible and well-circumscribed caudate nucleus tumors were produced using this stereotactic procedure.

Animals↗
PubMed1992

[Aortopulmonary fistula due to failed graft for aortic aneurysm].

Hemoptysis originating from an aortobronchial fistula is uncommon. This fistulous connection between the aorta and the lung usually results from a preexisting thoracic-aortic aneurysm, and is uniformly fatal when left untreated. However, with early diagnosis the survival rate exceeds 80%. The case of an aortobronchial fistula in a young alcoholic, 2 years after aortic aneurysmectomy, is presented. He was admitted with symptoms suggesting upper gastrointestinal bleeding, allegedly related to alcohol abuse. He died of a sudden, massive hemoptysis 5 days after admission. An aortobronchial fistula was found on autopsy. To diagnose aortobronchial fistula, a high index of suspicion is necessary. It should be considered in patients with hemoptysis after repair of a thoracic aneurysm.

Adult↗
PubMed1992

Oxygen utilisation by isopenicillin N synthase from Penicillium chrysogenum.

The enzyme isopenicillin N synthase (IPNS) converts delta-(L-alpha- aminoadipyl)-L-cysteinyl-D-valine (ACV) to isopenicillin N; an equimolar amount of oxygen is used in this oxidative ring closure reaction. Oxygen uptake rates of the reaction catalysed by partially purified IPNS from Penicillium chrysogenum SC 6140 and P2 were measured using an oxygen electrode. In contrast to published properties of Cephalosporium acremonium IPNS, the enzyme from P. chrysogenum was not stimulated by the addition of glutathione and showed reduced stimulation by Fe2+. The analysis of oxygen uptake rates showed the reaction to be first order with respect to oxygen concentration and the Km for ACV to be 0.4 mmol dm-3. The implications of these results for cell-free reactions using this enzyme and penicillin fermentations are discussed.

Biotechnology↗
PubMed1992

Attenuation of exercise induced asthma by local hyperthermia.

BACKGROUND: Prior treatment with local hyperthermia has been shown to prevent mast cell degranulation and leucocyte histamine release, and to reduce mortality and cellular infiltrates in a model of acute lung injury. Local hyperthermia is effective in reducing the symptoms of the common cold and perennial and seasonal allergic rhinitis, nasal patency also being improved in rhinitis. It is possible that these effects are mediated by common anti-inflammatory mechanisms, and that this treatment may be effective in the treatment of asthma. The effect of prior local hyperthermia on the response to exercise challenge and histamine bronchoprovocation was therefore examined. METHODS: In a randomised, double blind, placebo controlled, crossover study, 10 asthmatic subjects with exercise induced asthma used machines delivering 40 1/minute of fully humidified air at either 42 degrees C (active treatment) or 31 degrees C (placebo treatment) for 30 minutes' tidal breathing. For each pretreatment, at two week intervals they underwent exercise challenges starting one and 24 hours after starting the inhalations. After a further two weeks the protocol was repeated with histamine substituted for the exercise challenges. RESULTS: The mean (SE) maximum percentage fall in forced expiratory volume in one second (FEV1) was significantly lower one hour after treatment with air at 42 degrees C (30.8% (3.1%)) than after treatment with air at 31 degrees C (22.3% (2.9%)). There was no significant effect on exercise challenge at 24 hours, or on histamine challenge at either time point, though there were nonsignificant trends towards protection with exercise at 24 hours and with histamine at one hour. CONCLUSION: In asthmatic subjects the response to exercise challenge is significantly attenuated one hour after treatment with local hyperthermia. This treatment warrants further investigation in the treatment of clinical asthma and other inflammatory disorders.

Adolescent↗