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R Neal

Publications and source records attributed to R Neal.

At least 19 recordsLinked to original sources
PubMed2001

On the equilibrium between monomeric alpha-lactalbumin and the chaperoning complex of alpha-crystallin.

In chaperoning dithiothreitol-denatured alpha-lactabumin, alpha-crystallin forms a chaperoning complex. In order to study the kinetics of such chaperoning it needs to be established whether the formation of the chaperoning complex is a reversible or irreversible process. The chaperoning reaction was studied by dynamic light scattering as a function of concentration and weight ratio of alpha-lactalbumin/alpha-crystallin. HPLC and subsequent SDS-PAGE gel electrophoresis experiments established that the chaperoning complex formed contains both alpha-crystallin and alpha-lactalbumin. Upon rechromatographing the chaperoning complex, the presence of monomeric alpha-lactalbumin has been demonstrated in addition to the chaperoning complex itself. This and equilibrium dialysis experiments demonstrated conclusively the existence of an equilibrium between monomeric partially denatured alpha-lactalbumin and the chaperoning complex made of alpha-lactalbumin and alpha-crystallin.

Animals↗
PubMed2000

High performance liquid chromatography analysis of D-penicillamine by derivatization with N-(1-pyrenyl)maleimide (NPM).

D-Penicillamine (2-amino-3-mercapto-3-methylbutanoic acid), a well-known heavy metal chelator, is the drug of choice in the treatment of Wilson's disease and is also effective for the treatment of several disorders including rheumatoid arthritis, primary biliary cirrhosis, scleroderma, fibrotic lung diseases and progressive systemic sclerosis. The method proposed incorporates a technique, previously developed in our laboratory, that utilizes the derivatizing agent N-(1-pyrenyl)maleimide (NPM) and reversed-phase high-performance liquid chromatography (HPLC). The coefficients of variation for within-run precision and between-run precision for 500 nM standard D-penicillamine (D-pen) were 2.27% and 2.23%, respectively. Female Sprague-Dawley rats were given 1 g/kg D-pen i.p. and the amounts of D-pen in liver, kidney, brain and plasma were subsequently analyzed. This assay is rapid, sensitive and reproducible for determining D-pen in biological samples.

Animals↗
PubMed2000

A role for oxidative stress in suppressing serum immunoglobulin levels in lead-exposed Fisher 344 rats.

Evidence implicating oxidative stress in toxicity during lead intoxication in vivo has opened new avenues for investigation of the mechanisms of lead-induced immunosuppression. The current study explores the possibility that lead-induced oxidative stress contributes to the immunosuppression observed during lead poisoning. Fisher 344 rats were exposed to 2,000 ppm lead acetate in their drinking water for 5 weeks. One week following removal of lead from the drinking water, significant reductions in serum levels of IgA, IgM, and IgG were detected. Significant increases in oxidative damage, based on malondialdehyde (MDA) content, were observed in peripheral blood mononuclear cells (PMCs) collected during the same experiments. In addition, MDA content increased in livers from lead-exposed rats. Following 5 weeks of lead exposure, administration of either 5.5 mmol/kg N-acetylcysteine (NAC) or 1 mmol/kg meso-2,3-dimercaptosuccinic acid (DMSA) in the drinking water for 1 week significantly reversed the inhibitory effects of lead on serum immunoglobulin (Ig) levels. Also, all parameters indicative of oxidative stress returned to control levels. These results suggest that oxidative stress contributes to suppressed serum Ig levels during lead intoxication in vivo, and that intervention with either a thiol antioxidant (NAC) or a metal chelator (DMSA) will alleviate this lead-induced suppression by correcting the prooxidant/antioxidant imbalance caused by lead exposure.

Animals↗
PubMed2000

Socio-economic characteristics of adult frequent attenders in general practice: secondary analysis of data.

OBJECTIVE: This study was carried out to determine the effect of a range of socio-economic features on frequent attendance in general practice from a large database of general practice consultations using two definitions of frequent attendance. METHODS: Secondary analyses were carried out of data from the Fourth National Survey of Morbidity in General Practice covering 60 general practices in England and Wales. A total of 283 842 adult patients and their consultations between September 1991 and August 1992 were examined. The main outcome measure was the odds ratio of being a frequent attender (95% confidence intervals). RESULTS: Using a definition of 12+ consultations/year, men were less likely to be frequent attenders (OR 0.14, 95% CI 0.13-0.17); however, the difference between men and women lessens with age. Patients who were more likely to be frequent attenders included those who were divorced or widowed (1.41, 1.31-1.51); from social classes IIIM (1.23, 1.17-1.29) and IV/V (1.33, 1.26-1.41); South Asian people (1.38, 1.16-1.65); or unemployed (1.61, 1.46-1.77). Other factors signifying isolation or poverty were also linked to frequent attendance. Using the definition of '6+ consultations for minor problems' produced broadly similar results although the relative weight of the factors showed some differences. CONCLUSIONS: Socio-economic factors were important indicators of frequent attendance in general practice. Results were very similar using either definition, suggesting that both are valid for further work. Furthermore, frequent attendance is a complex process associated with many factors outside the control of the GP.

Adolescent↗
PubMed1999

The displacement, velocity and frequency profile of the frontal plane motion produced by the cervical lateral glide treatment technique.

OBJECTIVE: To investigate the specificity of linear and angular displacement, peak velocity and frequency of oscillation of the frontal plane motion produced by the lateral glide treatment technique of the cervical spine. DESIGN: A within-subjects design was used. BACKGROUND: The lateral glide treatment technique of the cervical spine has previously been shown to produce specific neurophysiological effects, whereas the technique's biomechanical effects remain uninvestigated. A relationship may exist between a technique's biomechanical effects and its clinical outcome. METHODS: Eight asymptomatic subjects participated in the study. Retroreflective markers were placed dorsally at the occiput, and the C5, T1, T3 and T5 vertebrae. Movement of these markers was recorded by a video processor. The same physiotherapist applied the treatment technique to each subject. RESULTS: Linear displacement (3.336 cm) and peak velocity (13.643 cm/s) between C5 and T1 markers was greater than between T1 and T3, Occiput and C5, and T3 and T5. Angular displacement about C5 (26.5 degrees ) was twice that about T1 and T3, but unlike T1 and T3 occurred in the opposite direction to that of the treatment technique. Frequency of oscillation was 1. 255 Hz. CONCLUSION: The lateral glide treatment technique produced a characteristic ipsilateral displacement rather than side flexion, predominantly at its region of application. RELEVANCE: This study provides the basis for further investigations of the mechanisms of action of the lateral glide treatment technique. It also provides clinicians with guidelines for the application of this technique.

Adolescent↗
PubMed1999

Effects of some sulfur-containing antioxidants on lead-exposed lenses.

Lead (Pb) is known to negatively affect glutathione (GSH) metabolism in the lens. The present study examined the effects of Captopril, Taurine, and alpha-Lipoic acid on the Pb-induced GSH depletion and lipid peroxide increase in the lenticular system. Captopril administration returned the GSH, cysteine (CYS), and malondialdehyde (MDA) levels to near normal. Following Taurine administration the GSH, CYS and MDA levels were intermediate between the control group and the Pb group levels. Alpha-Lipoic acid administration, however, only increased the CYS levels. No significant changes in oxidized glutathione (GSSG) levels were observed in any treatment group.

Animals↗
PubMed1999

Captopril as an antioxidant in lead-exposed Fischer 344 rats.

Recent studies suggest that lead induces oxidative stress in various tissues. Captopril ([2S]-1-[3-mercapto-2-methylpropionyl]-L-proline), an angiotensin-converting enzyme inhibitor, is a well-known antihypertensive agent and is also believed to function as an antioxidant. In the present study the antioxidant effect of captopril on lead-induced oxidative stress was studied in Fischer 344 rats. Their liver, brain and kidneys were assayed for glutathione (GSH), glutathione disulfide (GSSG), malondialdehyde concentrations, and catalase activities. The results from animals treated with captopril were compared to results of control and lead-exposed non-treated groups. The captopril-treated samples showed higher GSH:GSSG ratios in the liver, brain and kidneys, as well as slightly decreased malondialdehyde concentrations. The catalase activity was not significantly affected.

3,4-Methylenedioxyamphetamine↗
PubMed1998

Effects of N-acetylcysteine and 2,3-dimercaptosuccinic acid on lead induced oxidative stress in rat lenses.

Lead (Pb) is known to disrupt the pro-oxidant/anti-oxidant balance of tissues which leads to biochemical and physiological dysfunction. The present study investigated the effects of exposure on the redox status of the lenses of Fisher 344 rats and examined whether antioxidant or chelator administration reversed these changes. Animals were given 5 weeks of 2000 ppm Pb exposure followed by 1 week of either antioxidant, chelator or distilled water administration. Glutathione (GSH) and cysteine (CYS) levels decreased in the Pb-exposed group. N-acetylcysteine or 2,3-dimercaptopsuccinic acid (Succimer) supplementation following Pb intoxication resulted in increases in the GSH and CYS levels. Protein bound glutathione (PSSG) and cysteine (PSSC) increased following Pb exposure. In the Succimer-treated animals, the PSSG decreased significantly. The glutathione disulfide (GSSG) levels remained unchanged. Malondialdehyde (MDA) levels, a major lipid peroxidation byproduct, increased following Pb exposure and decreased following Succimer treatment. Our results suggest that antioxidant supplementation, as well as chelation, following Pb exposure may enhance the reductive status of lenses.

Acetylcysteine↗
PubMed1998

Antioxidant effects of N-acetylcysteine and succimer in red blood cells from lead-exposed rats.

This study examined whether lead-induced alterations in selected parameters that are indicative of oxidative stress accompany the toxic effects of lead in red blood cells (RBCs) in vivo. It also explored the possibility that treatment with N-acetylcysteine (NAC) or succimer (meso-2,3-dimercaptosuccinic acid) was capable of reversing parameters indicative of lead-induced oxidative stress. Fisher 344 rats were given 2000 ppm lead acetate in their drinking water for 5 weeks. The lead was then removed and the animals were given NAC (800 mg/kg/day) or succimer (90 mg/kg/day) in their drinking water for 1 week, after which the RBCs were harvested. Animals not given lead and those given lead, but not NAC or succimer, served as negative and positive controls, respectively. At the end of the experiment, blood-lead levels were 35 +/- 4 microg/dl in lead-treated animals, which were reduced to 2.5 +/- 1 microg/dl by treatment with succimer and to 25 +/- 3 microg/dl by treatment with NAC. Lead-exposed animals demonstrated signs of anemia as evidenced by anisocytosis, poikilocytosis, and alterations in hemoglobin, hematocrit, and mean corpuscular volume. Lipid peroxidation, as evidenced by increased malondialdehyde (MDA) content, as well as decreases in reduced glutathione (GSH) and increases in catalase and glucose 6-phosphate dehydrogenase (G6PD) activity were noted in RBCs from lead-treated rats, suggesting that the lead induced oxidative stress. In addition, a significant reduction in blood delta-aminolevulinic acid dehydratase (ALAD) activity suggested that accumulation and autooxidation of delta-aminolevulinic acid might contribute to lead-induced oxidative stress. Treatment with either NAC or succimer reversed lead-induced alterations in MDA and GSH content, but only succimer appeared to partially restore ALAD activity. These results provide in vivo evidence supporting the hypothesis that lead induces oxidative stress in RBCs, which is reversible by treatment with a thiol antioxidant (NAC), as well as a chelating agent (succimer).

Acetylcysteine↗
PubMed1997

Pro-oxidant effects of delta-aminolevulinic acid (delta-ALA) on Chinese hamster ovary (CHO) cells.

delta-Aminolevulinic Acid (delta-ALA) is a heme precursor accumulated in lead poisoning and acute intermittent porphyria. Although no single mechanism for lead toxicity has yet been defined, recent studies suggest at least some of the lead-induced damage may originate from delta-ALA-induced oxidative stress. The present study was designed to test the hypothesis that delta-ALA accumulation in Chinese hamster ovary (CHO) cells contributes to the cumulative oxidative challenge of lead poisoning as indicated by the oxidative stress parameters glutathione (GSH), glutathione disulfide (GSSG), malondialdehyde equivalents (MDA), and catalase (CAT). It will also examine the possibility that this oxidative challenge can be reversed by treatment with an antioxidant such as N-acetylcysteine (NAC). First in vitro administration of delta-ALA to CHO cells was found to have a concentration-dependent inhibitory effect on colony formation and cell survival. NAC administration was shown to alleviate this inhibition in CHO survival. The oxidative status of CHO cell cultures exposed to increasing concentrations of delta-ALA was then examined. Decreases in GSH levels (P < 0.05) were observed in the delta-ALA-treated cultures as compared to the controls, while GSSG and MDA levels were significantly increased in delta-ALA-treated cells (P < 0.05). CAT activity was not significantly affected. NAC administration concurrent with delta-ALA exposure resulted in GSH and GSSG levels similar to the control levels, while no significant improvement in MDA was observed. These results indicate a state of oxidative stress and suggest that the delta-ALA- induced inhibitory effect on CHO colony formation may be due to its pro-oxidant effect. To assess whether this oxidative challenge would induce antioxidant increases during extended exposure to delta-ALA, CHO cells were exposed to 5 mM delta-ALA for increasing time periods. The GSH and GSSG levels were measured and a rebound effect was observed after 12 h of delta-ALA exposure.

Aminolevulinic Acid↗
PubMed1992

A force-indentation relationship for gymnastic mats.

The mechanical properties of a series of gymnastic surfaces are investigated. A Force--Indentation relationship is obtained for each surface. This law can be used to simulate the ground reaction force during under-foot impact with a gymnastic surface. The law is independent of many of the properties of the striking body and when incorporated into a system of differential equations describing the motion of the impacting body, can be used to compute system responses and to investigate the importance of different properties of the various surfaces. Several examples, using both a single, rigid mass and a four link, articulated system are presented, and demonstrate that the relationship can be satisfactorily incorporated into a solution algorithm for a large-displacement dynamical analysis.

Acceleration↗
PubMed1990

The empires strike back. Broken promises: Columbia-Presbyterian Medical Center. Ignoring the community's needs: St. Luke's-Roosevelt Hospital Center.

In the fall of 1985 in an issue titled "Fighting Back Against the Empires" (Vol. 16, No. 5), Health/PAC reported on the plans of four of New York City's academic medical center "empires" for major expansion. The focus of our coverage was the efforts of two of the communities served by these institutions to ensure that the plans were responsive to their needs. At the time, we were cautiously optimistic that these events were signs that "although the empires still dominate New York City's health care system, they no longer rule unchallenged." In the past six months, the plans of two of these institutions, Columbia-Presbyterian Medical Center and St. Luke's-Roosevelt Hospital Center, warrant another look at the success of the efforts to hold the major medical centers responsible for the welfare of the communities in which they are located.

Academic Medical Centers↗