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Biomedical subjects

J Penny

Publications and source records attributed to J Penny.

At least 19 recordsLinked to original sources
PubMed2003

Effect of Loxosceles gaucho venom on cell morphology and behaviour in vitro in the presence and absence of sphingomyelin.

This study was performed to investigate whether the toxic effects of Loxosceles gaucho venom on cells might be exerted via stimulators of TNF-alpha release generated by sphingomyelinase D--a major component of the venom. It was demonstrated that L. gaucho venom alone is unable to induce TNF-alpha release by J774A.1 cells, while in the presence of exogenous sphingomyelin it induces a high level of TNF-alpha release which is significantly increased by incubation with non-inactivated serum. Ceramide phosphate also induces TNF-alpha release in J774A.1 cells, but (unlike sphingomyelin/sphingomyelinase) the level of release is not influenced by the presence or otherwise of non-inactivated serum. L. gaucho venom does not induce proliferation of J774A.1 cells and even at high concentrations it does not affect their viability. J774A.1 cells, which prior to venom treatment were elongated and clumped, round up after venom treatment, but, revert to their original morphology after incubation with fresh medium. TNF-alpha resistant MRC-5 cells and TNF-alpha sensitive MCF-7 cells are susceptible to the toxic effect of both L. gaucho venom and ceramide phosphate. The results obtained in this study demonstrate that exogenous sphingomyelin can modulate, in vitro, the release of TNF-alpha induced by L. gaucho venom in mouse macrophages. In addition, the results also indicate that ceramide phosphate and L. gaucho venom are toxic to several different cell types, via a variety of mechanisms, some, but not all, of which may involve TNF-alpha as an intermediary.

Animals↗
PubMed2003

The influence of surface modification on the cytotoxicity of PAMAM dendrimers.

The influence of surface modification on the cytotoxicity of PAMAM dendrimers was examined using Caco-2 cells. Dendrimers were modified by conjugating either lauroyl chains or polyethylene glycol (PEG) 2000 onto the surface of cationic PAMAM dendrimers (G2, G3, G4). The cytotoxicity of unmodified dendrimers towards Caco-2 cells was appreciably higher for cationic (whole generation) compared with anionic (half generation) dendrimers and for both types increased with increasing size (generation) and concentration. A marked decrease in the cytotoxicity of cationic PAMAM dendrimers was noted when the surface was modified, with the addition of six lauroyl or four PEG chains being particularly effective in decreasing cytotoxicity. This decrease in cytotoxicity is thought to be due to a reduction/shielding of the positive charge on the dendrimer surface by the attached chains. The cytotoxicity of dendrimer-based delivery systems is likely to be very different from the parent dendrimer.

Caco-2 Cells↗
PubMed2003

Influence of sphingomyelin and TNF-alpha release on lethality and local inflammatory reaction induced by Loxosceles gaucho spider venom in mice.

It is well known that Loxosceles venom induces local dermonecrosis in rabbits, guinea pigs and humans but not in mice, although, depending on the dose, Loxosceles venom can be lethal to mice. In this work we demonstrate that mice injected intradermally in the dorsal area of the back can survive a lethal dose of Loxosceles gaucho venom and also develop an inflammatory reaction (with infiltration of leukocytes shown by histological analysis) at the local injection site when the venom is co-administered with sphingomyelin. It was observed that more venom was retained for a longer period of time at the local injection site when venom was co-administered with sphingomyelin. The presence of exogenous sphingomyelin did not influence significantly the release of TNF-alpha induced by L. gaucho venom. These results suggest that the action of venom on sphingomyelin, producing ceramide phosphate, causes the development of an inflammatory reaction, which in turn traps the venom in the local area for a long period of time and does not allow it to disperse systemically in a dose sufficient to cause death. Our findings also indicate that the size and availability of the local sphingomyelin pool may be important in determining the outcome of Loxosceles envenoming in different mammalian species.

Animals↗
PubMed2001

Expression and functional characterization of a Plasmodium falciparum Ca2+-ATPase (PfATP4) belonging to a subclass unique to apicomplexan organisms.

We have obtained a full-length P type ATPase sequence (PfATP4) encoded by Plasmodium falciparum and expressed PfATP4 in Xenopus laevis oocytes to study its function. Comparison of the hitherto incomplete open reading frame with other Ca(2+)-ATPase sequences reveals that PfATP4 differs significantly from previously defined categories. The Ca(2+)-dependent ATPase activity of PfATP4 is stimulated by a much broader range of [Ca(2+)](free) (3.2-320 micrometer) than are an avian SERCA1 pump or rabbit SERCA 1a (maximal activity < 10 micrometer). The activity of PfATP4 is resistant to inhibition by ouabain (200 micrometer) or thapsigargin (0.8 micrometer) but is inhibited by vanadate (1 mM) or cyclopiazonic acid (1 microM). We used a quantitative polymerase chain reaction to assay expression of mRNA encoding PfATP4 relative to that for beta-tubulin in synchronized asexual stages and found variable expression throughout the life cycle with a maximal 5-fold increase in meronts compared with ring stages. This analysis suggests that PfATP4 defines a novel subclass of Ca(2+)-ATPases unique to apicomplexan organisms and therefore offers potential as a drug target.

Amino Acid Sequence↗
PubMed1999

Comparison of auscultatory and oscillometric automated blood pressure monitors in the setting of preeclampsia.

OBJECTIVE: The aim of this study was to compare the accuracy of 2 automated blood pressure monitors against mercury sphygmomanometry and intra-arterial blood pressure determination in women with preeclampsia. STUDY DESIGN: The auscultatory and oscillometric monitors were compared with mercury sphygmomanometry according to the British Hypertension Society protocol and criteria of the Association for the Advancement of Medical Instrumentation in a group of 30 women with proteinuric preeclampsia. In addition both monitors were compared with intra-arterial blood pressure measurements in a group of 6 women with severe preeclampsia. The mean (+/- SD) of the differences was calculated and a paired t test was used to compare values obtained with each monitor with intra-arterial measurements. RESULTS: Compared with mercury sphygmomanometry the auscultatory QuietTrak monitor markedly underestimated systolic and diastolic blood pressure by 13 +/- 15 mm Hg. The oscillometric SpaceLabs 90207 monitor also underestimated systolic pressure by 10 +/- 10 mm Hg and diastolic pressure by 8 +/- 7 mm Hg. According to the British Hypertension Society grading criteria both monitors achieved the lowest grade (D) for recording systolic and diastolic pressure. The 2 monitors also did not meet the accuracy criteria stipulated by the Association for the Advancement of Medical Instrumentation. Compared with intra-arterial readings the SpaceLabs monitor significantly underestimated systolic and mean arterial pressures (by 19 and 7 mm Hg, respectively, P <. 01). The QuietTrak monitor significantly underestimated systolic, diastolic, and mean arterial pressures (by 25 mm Hg, P <.05, 18 mm Hg, P <.01, and 20 mm Hg, P <.01, respectively). CONCLUSION: Neither monitor can be recommended for clinical use in women with proteinuric preeclampsia.

Auscultation↗
PubMed1998

Do hospital palliative care teams improve symptom control? Use of a modified STAS as an evaluation tool.

The support team assessment schedule (STAS) has previously been validated as an evaluation tool for community palliative care teams and inpatient units. This study reports on use of an expanded STAS (E-STAS) to determine symptom prevalence and outcome for inpatients and outpatients referred to a multiprofessional hospital palliative care team. E-STAS forms were completed on patients at referral and twice weekly thereafter. Between August 1996 and May 1997, 352 patients had one or more E-STAS forms completed; 122 of this group had three or more assessments. One-hundred-and-eighty-two patients were male and 170 were female, the median age was 68.5 years (range 26-101 years) and all but 27 (8%) had malignant disease. Of the symptoms assessed on referral, the most common were psychological distress 93%, anorexia 73%, pain 59%, mouth discomfort 59%, depression 40%, constipation 36%, breathlessness 32%, nausea 24% and vomiting 13%. In the 122 patients where three or more assessment were completed, statistically significant improvements from first to last assessment were seen in all symptoms except depression. This study suggests that E-STAS may be a useful tool to evaluate interventions by a hospital palliative care team in patients with advanced disease.

Adult↗
PubMed1997

The pathomorphologic changes that accompany the resolution of cervical radiculopathy. A prospective study with repeat magnetic resonance imaging.

STUDY DESIGN: A prospective study with independent clinical and radiologic review. OBJECTIVE: To assess whether regression of cervical intervertebral disc herniations accompanied and correlated with clinical improvement in patients recovering from cervical radiculopathy without undergoing surgical intervention. SUMMARY OF BACKGROUND DATA: The study subjects were 13 consecutive patients, nine men (69%) and four women (31%), presenting with cervical radiculopathy. All patients but one had objective neurologic signs. All patients had large posterolateral cervical intervertebral disc herniations demonstrated by magnetic resonance imaging. METHODS: Pain was controlled by serial periradicular and epidural corticosteroid injections. Patients were finally examined and discharged from care because of sustained pain control at an average of 6 months (range, 2-12 months). They were interviewed subsequently over the telephone by an independent clinician and rescanned at an average of 12 months (range, 4-31 months). The scans were reviewed by an independent radiologist masked to the sequence of the scans. RESULTS: Regression of cervical disc herniations was demonstrated in 12 of the 13 patients. All patients had made a satisfactory clinical recovery, but the one with the herniation that had not regressed suffered from persistent minor symptoms. CONCLUSIONS: Most cervical disc herniations regress with time and without the need for surgical resection. Thus, surgical intervention can be avoided with adequate pain control, allowing the herniation time to regress.

Adrenal Cortex Hormones↗
PubMed1992

Changes in the CA 19-9 antigen and Lewis blood group with pulmonary disease severity in cystic fibrosis.

The altered carbohydrate structure of sputum from patients with cystic fibrosis (CF) has been thought to be due to the inflammatory airway response. Carcinoembryonic antigen (CEA) and CA 19-9 detect sialosylated carbohydrates in mucus. The epitope of CA 19-9 is part of the Lewis A (Le(a)) blood group antigen. Serum concentrations of CEA and CA 19-9 were determined by radioimmunoassay in 41 CF patients, aged 6-34 years; 16 were asymptomatic Outpatients, and 25 had been admitted for pulmonary exacerbations. There was no difference in CEA between groups. The CA 19-9 serum concentration was elevated in 90% of patients who had at least one of the two Lewis antigens. The CA 19-9 concentration of Inpatients with exacerbations was 2.7 times that of stable Outpatients (263 +/- 44 versus 99 +/- 13 U/mL; P less than 0.02). CA 19-9 correlated significantly with age (r = 0.35, P less than 0.05), Brasfield score (r = 0.39, P less than 0.015), pulmonary function tests, cough severity (r = 0.50, P less than 0.001) and NIH clinical score (r = 0.57, P less than 0.001). CA 19-9 concentration of Inpatients decreased by 44% from admission to discharge (302 +/- 45 to 169 +/- 39, P less than 0.02). Fourteen of 25 (56%) of the Inpatients were Le(a) positive versus only 3/15 (20%) of Outpatients who had milder lung disease (P less than 0.002). Of the Inpatients, 25% with more advanced lung disease were Le(a+b+), a rare blood group in the normal population, and one not observed in the Outpatients with milder disease.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1991

Mechanisms of phosphate transport in sheep intestine and parotid gland: response to variation in dietary phosphate supply.

The transport of phosphate in intestinal brush-border membrane and parotid basolateral membrane vesicles isolated from sheep maintained on high and low phosphate diets have been studied. The mechanism of the transport of phosphate in the intestine is via a proton symporter whilst in the parotid gland it is effected by a Na+ coupled transporter. In sheep fed a low-P diet there is no change in the capacity of the parotid basolateral membrane to transport phosphate into the parotid end piece cells. This is in marked contrast to the response of the enterocyte brush-border membrane, where there is a significant enhancement of the capacity of the membrane to transport phosphate. We conclude that in sheep the gut appears to play a major role in response to phosphate deprivation, by increasing the capacity to transport phosphate. This enhancement is not achieved by increases in the levels of circulating 1,25-dihydroxycholecalciferol.

Animals↗