PubMed Health⌕ Search

Biomedical subjects

N Hall

Publications and source records attributed to N Hall.

At least 37 records · Page 2Linked to original sources
PubMed1998

Structural and functional changes in proteins induced by free radical-mediated oxidative stress and protective action of the antioxidants N-tert-butyl-alpha-phenylnitrone and vitamin E.

The free radical theory of aging proposes that reactive oxygen species (ROS) cause oxidative damage over the lifetime of the subject. It is the cumulative and potentially increasing amount of accumulated damage that accounts for the dysfunctions and pathologies seen in normal aging. We have previously demonstrated that both normal rodent brain aging and normal human brain aging are associated with an increase in oxidative modification of proteins and in changes in plasma membrane lipids. Several lines of investigation indicate that one of the likely sources of ROS is the mitochondria. There is an increase in oxidative damage to the mitochondrial genome in aging and a decreased expression of mitochondrial mRNA in aging. We have used a multidisciplinary approach to the characterization of the changes that occur in aging and in the modeling of brain aging, both in vitro and in vivo. Exposure of rodents to acute normobaric hyperoxia for up to 24 h results in oxidative modifications in cytosolic proteins and loss of activity for the oxidation-sensitive enzymes glutamine synthetase and creatine kinase. Cytoskeletal protein spin labeling also reveals synaptosomal membrane protein oxidation following hyperoxia. These changes are similar to the changes seen in senescent brains, compared to young adult controls. The antioxidant spin-trapping compound N-tert-butyl-alpha-phenylnitrone (PBN) was effective in preventing all of these changes. In a related study, we characterized the changes in brain protein spin labeling and cytosolic enzyme activity in a series of phenotypically selected senescence-accelerated mice (SAMP), compared to a resistant line (SAMR1) that was derived from the same original parents. In general, the SAM mice demonstrated greater oxidative changes in brain proteins. In a sequel study, a group of mice from the SAMP8-sensitive line were compared to the SAMR1-resistant mice following 14 days of daily PBN treatment at a dose of 30 mg/kg. PBN treatment resulted in an improvement in the cytoskeletal protein labeling toward that of the normal control line (SAMR1). The results of these and related studies indicate that the changes in brain function seen in several different studies may be related to the progressive oxidation of critical brain proteins and lipids. These components may be critical targets for the beneficial effects of gerontotherapeutics both in normal aging and in disease of aging.

Adult↗
PubMed1998

Improved ultrasound detection of renal scarring in children following urinary tract infection.

A system for defining renal scarring on ultrasound is proposed and compared with DMSA scintigraphy. Renal scarring was assessed with ultrasound in children following urinary tract infection (UTI) using the following criteria: (1) proximity of sinus echoes to cortical surface; (2) loss of pyramids; (3) irregularity of outline; (4) loss of definition of capsular echo; and (5) calyceal dilatation. Three hundred and thirty-nine consecutive ultrasound scans (US) and DMSA scintigrams, comprising 648 kidneys, were performed and reported blindly and the results were compared. Using DMSA scintigraphy as the gold standard, ultrasound had a positive predictive value of 93% and a negative predictive value of 95%. Ultrasound disagreed with DMSA scintigraphy in 5.2% of kidneys. On review of the cases of disagreement where arbitration was possible by comparison with other imaging, ultrasound was incorrect in 10 kidneys and DMSA was incorrect in 13. We conclude that the sensitivity in the ultrasound detection of renal scarring can be greatly improved using this method. If no scars were detected at ultrasound an alternative explanation for an abnormal DMSA scintigram should be sought.

Adolescent↗
PubMed1998

Visual acuity and its relationship to early growth, eye disease, and aging in north Hertfordshire.

We investigated the relationship between visual acuity, early growth and eye disease in a retrospective cohort study of 700 individuals in North Hertfordshire. Records of birth weight and weight at one year were used to determine early growth. We measured visual acuity and age-related eye diseases using standard instruments in those same individuals (now aged 63 to 73). Visual acuity below the legal threshold for driving in the UK (6/11 or poorer) was present in 13% of subjects. There was no clear association between birth weight or weight at one year and visual acuity. Vision impairment was found to be associated with refractive error, cataract, age-related maculopathy, and elevated macular threshold. After controlling for the effects of eye disease, increasing age remained a significant predictor of poorer visual acuity.

Aged↗
PubMed1997

2'-Substitution of cocaine selectively enhances dopamine and norepinephrine transporter binding.

Few studies have characterized the effect of substituents at the 2'-position of cocaine on transporter binding potency and selectivity. We synthesized 2'-OH-, 2'-F- and 2'-acetoxy-cocaines and compared their binding potencies for rat dopamine, norepinephrine and 5-hydroxytryptamine transporters to cocaine, 3'-OH-, 4'-OH-, 2'-OH,4'-I-cocaine derivatives, and to the transporter selective ligands WIN 35,428, nisoxetine and paroxetine. Unlike most substitutions, 2'-OH- and 2'-acetoxy-groups increased cocaine's binding potency for the dopamine transporter (10- and 4-fold, respectively). These substituents also enhanced binding to the norepinephrine transporter (52- and 35-fold, respectively) but had less effect on 5-hydroxytryptamine transporter binding. 2'-Hydroxylation also enhanced binding of 4'-I cocaine, an analog with low DA binding potency. The ability of 2'-substituents to substantially increase cocaine binding potency and to alter selectivity for brain transporters indicates the potential importance of the 2'-position in transporter binding.

Animals↗
PubMed1997

TNF-mediated cytotoxicity of L929 cells: role of staurosporine in enhancement of cytotoxicity and translocation of protein kinase C isozymes.

The role of protein kinase C (PKC) in tumour necrosis factor (TNF)-mediated cytotoxicity was investigated, using the L929 cell line. The PKC activator phorbol-12-myristate 13-acetate (PMA) increased proliferation and inhibited TNF-induced cytotoxicity of L929 cells. A range of specific PKC inhibitors had no effect on TNF-mediated killing, suggesting that PKC does not play a direct role in this response. However, staurosporine enhanced cytotoxicity by TNF in the presence of actinomycin D, a protein synthesis inhibitor. In view of this finding, the authors investigated the role of specific PKC isozymes in both TNF-mediated cytotoxicity and staurosporine-induced sensitization to killing. PKC-alpha, beta, epsilon and zeta were detected in L929 cells. PKC-beta was only weakly detected in the cytoplasm, PKC alpha, epsilon and zeta were all found in resting cytoplasm and membrane. Stimulation with PMA caused a strong translocation of PKC-alpha but not zeta to the membrane. TNF had no effect on these isozymes but interestingly caused a translocation of PKC-epsilon, which also occurred in response to PMA. Staurosporine caused a translocation of PKC-zeta to the plasma membrane and a loss of PKC-epsilon from the cytosol. Although TNF induced PKC-epsilon translocation, this is unlikely to be involved in cytotoxicity as this effect was also induced by PMA which protected against TNF-mediated cytotoxicity. Staurosporine also induced translocation of PKC-zeta, an isozyme whose activity was previously found to be resistant to inhibition by staurosporine. These findings suggest the possibility that the mechanism by which staurosporine potentiates TNF action does not involve inhibition of PKC, but in contrast may involve modulation of PKC-zeta.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1997

Caring for the patient with interstitial cystitis.

Interstitial cystitis (IC) is a chronic, painful, debilitating bladder disorder which predominantly affects women. The etiology of IC is unknown, the diagnosis is difficult to make, and treatments are aimed at minimizing symptoms. IC affects every aspect of an individual's life. Both generalist and advanced practice nurses play a vital role in enhancing the IC patient's quality of life through emotional support and education.

Adult↗
PubMed1996

Occupational risk factors for developing tuberculosis.

We sought to assess whether there is an increased risk of tuberculosis among individuals who work in certain industries or occupations. A case-referent study of 149 male tuberculosis (TB) patients reported to the New Jersey Health Department from 1985 to 1987 and 290 referents was performed. Standardized interviews were conducted via the telephone or in person. Increased risk of TB was highest in heavy drinkers (OR = 3.33, 95% CL 1.99-5.59) and those who had a history of living with someone who had a history of TB (OR = 10.92, 95% CL 4.92-24.22). Occupations and industries associated with elevated risk for TB included: four silica-using industries-quarrying (OR = 3.96, 95% CL 0.36-44.02), pottery and related products (OR = 1.99, 95% CL 0.49-8.06), nonmetallic mineral and stone products (OR = 4.00, 95% CL 0.72-22.10), and ship and boat building and repair (OR = 1.84, 95% CL 0.76-4.43); hospitals (OR = 2.10, 95% CL 1.08-4.10); light truck drivers (OR = 2.49, 95% CL 1.30-4.77); agriculture (OR = 2.31, 95% CL 0.82-6.50); eating and drinking establishments (OR = 2.83, 95% CL 1.11-7.20); and janitors/cleaners (OR = 2.00, 95% CL 0.63-6.31). Except for janitors/cleaners, these elevated odds ratios remained for the above occupations/industries after controlling for alcohol or a history of having lived with someone with tuberculosis. Limitations of the study include a poor response rate (38%) and the exclusion of women from the study.

Alcohol Drinking↗
PubMed1996

Microsatellite instability in follicle centre cell lymphoma.

Fluorescent polymerase chain reaction (PCR) was used to assay 12 microsatellite markers (APC x 2, DCC, P53 x 2, RB1, NM23, WT1, D6S260, D6S262, D6S281 and TNFa) to look for evidence of microsatellite instability in 40 cases of follicle centre cell lymphoma (FCC). Evidence of novel alleles seen in the tumour tissue but not the normal uninvolved tissue was seen in seven cases (17%). In only two of these cases (5%) was more than one locus involved but in these cases multiple affected loci were seen (4/12 and 7/12 respectively). The detection of microsatellite instability indicates a DNA repair defect such as that which would be predicted to occur in cells with mutated mismatch repair genes, a novel finding in FCC lymphoma.

Chromosomes, Human, Pair 14↗
PubMed1996

Effects of antigen presentation on superantigen-induced apoptosis mediated by Fas/Fas ligand interactions in human T cells.

Stimulation of T cells with bacterial superantigens has several distinct functional outcomes including proliferation, anergy and apoptosis. At present however, the mechanisms that dictate whether activation, anergy, or apoptosis predominate are unclear. In this study we have investigated the effects of superantigen presentation to mature superantigen-reactive human T-cell lines. Despite expressing major histocompatibility complex (MHC) class II molecules, these lines failed to proliferate in response to superantigen in the absence of antigen-presenting cells (APC) but proliferated when minimal APC were added. In the absence of APC a significant proportion of the T cells underwent apoptosis. This response was rapid, antigen dependent and largely abolished by the addition of cyclosporin A. Interestingly the response was not blocked by the addition of a number of antibodies to cell surface molecules including MHC class II and intracellular adhesion molecule-1. Using both a bioassay and messenger RNA analysis we were able to demonstrate that stimulation of these T cells with superantigen resulted in the induction of Fas-ligand expression on the T cells and furthermore, the ability of these cells to induce apoptosis was inhibited by the addition of blocking Fas antibodies as well as a Fas-Fc fusion protein. These data demonstrate that stimulation of T cells with staphylococcal enterotoxin B induces expression of Fas-ligand resulting in T-cell apoptosis; however, the final outcome of proliferation or apoptosis is determined by the presence of APC.

Antigen Presentation↗
PubMed1996

The effect of interferon-alpha on the pituitary-adrenal axis.

This report concerns the use of a minimum stress animal model for evaluating the neuromodulatory effects of interferon-alpha (IFN-alpha). Male Sprague-Dawley rats, 350-450 g, received jugular catheters and were habituated to handling and sampling arenas. These procedures will minimize stress usually associated with i.v. injections and blood sampling. Natural rat IFN-alpha/beta (RaIFN-alpha/beta) endotoxin free (Lee Biomolecular Research Laboratories, San Diego, CA) or recombinant human IFN-alpha, (rHuIFN-alpha) (a gift from Hoffman La Roche, Nutley, NJ) was injected into rats via catheter at various IFN concentrations. Controls were injected with either (1) vehicle (saline), (2) human or bovine serum albumin in saline, or (3) heat-denatured RaIFN-alpha/beta. Experiments were begun (0 h) at about 0900 h, and blood samples were withdrawn at intervals up to 2 h after IFN or control injections and replaced by the same volume of saline. The concentrations of corticosterone and ACTH in peripheral plasma were measured by radioimmunoassay. Both IFN, when injected at concentrations of 300 or 600 U/g body weight (U/gbw), stimulated an increase above 0 h levels of both hormones in the same animals. Additionally, the stimulation was also evident when compared with plasma hormone levels in animals injected with control substance in a parallel time course. After administration of 150 U/gbw of either IFN, only the increase in the blood corticosterone was significant. These studies demonstrate that both homospecific (RaIFN-alpha/beta) and heterospecific (rHuIFN-alpha) IFN preparations are capable of stimulating the pituitary-adrenal axis.

Adrenal Cortex↗
PubMed1996

Microtubular proteolysis in focal cerebral ischemia.

Calpain, a neutral protease activated by calcium, may promote microtubular proteolysis in ischemic brain. We tested this hypothesis in an animal model of focal cerebral ischemia without reperfusion. The earliest sign of tissue injury was observed after no more than 15 min of ischemia, with coiling of apical dendrites immunolabeled to show microtubule-associated protein 2 (MAP2). After 6 h of ischemia, MAP2 immunoreactivity was markedly diminished in the infarct zone. Quantitative Western analysis demonstrated that MAP2 was almost unmeasurable after 24 h of ischemia. An increase in calpain activity, shown by an antibody recognizing calpain-cleaved spectrin fragments, paralleled the loss of MAP2 immunostaining. Double-labeled immunofluorescent studies showed that intraneuronal calpain activity preceded evidence of MAP2 proteolysis. Perikaryal immunolabeling of tau protein became increasingly prominent between 1 and 6 h in neurons located within the transition zone between ischemic and unaffected tissue. Western blot experiments confirmed that dephosphorylation of tau protein occurred during 24 h of ischemia, but was not associated with significant loss of tau antigen. We conclude that focal cerebral ischemia is associated with early microtubular proteolysis caused by calpain.

Animals↗
PubMed1995

Brain regional correspondence between Alzheimer's disease histopathology and biomarkers of protein oxidation.

Four biomarkers of neuronal protein oxidation [W/S ratio of MAL-6 spin-labeled synaptosomes, phenylhydrazine-reactive protein carbonyl content, glutamine synthetase (GS) activity, creatine kinase (CK) activity] in three brain regions [cerebellum, inferior parietal lobule (IPL), and hippocampus (HIP)] of Alzheimer's disease (AD)-demented and age-matched control subjects were assessed. These endpoints indicate that AD brain protein may be more oxidized than that of control subjects. The W/S ratios of AD hippocampal and inferior parietal synaptosomes are 30 and 46% lower, respectively, than corresponding values of tissue isolated from control brain; however, the difference between the W/S ratios of AD and control cerebellar synaptosomes is not significant. Protein carbonyl content is increased 42 and 37% in the Alzheimer's HIP and IPL regions, respectively, relative to AD cerebellum, whereas carbonyl content in control HIP and IPL is similar to that of control cerebellum. GS activity decreases an average of 27% in the AD brain; CK activity declines by 80%. The brain regional variation of these oxidation-sensitive biomarkers corresponds to established histopathological features of AD (senile plaque and neurofibrillary tangle densities) and is paralleled by an increase in immunoreactive microglia. These data indicate that senile plaque-dense regions of the AD brain may represent environments of elevated oxidative stress.

Aged↗
PubMed1995

Expression of CD44 on rheumatoid synovial fluid lymphocytes.

OBJECTIVES: To investigate the involvement of the adhesion molecule CD44 in the homing of lymphocytes to synovial tissue, by examining the density of expression and molecular mass of CD44 on rheumatoid synovial fluid lymphocytes. METHODS: Twenty patients with rheumatoid arthritis were studied. Peripheral blood and synovial fluid lymphocytes were isolated by Ficoll-Hypaque sedimentation. CD44 expression was analysed by two colour flow cytometry of CD3 positive T lymphocytes with calculation of mean fluorescence intensity. Expression of activation markers M21C5, M2B3, interleukin (IL)-2 receptor and transferrin receptor was quantitated. In addition, CD44 molecular mass was examined by Western blot in six patients. RESULTS: CD44 expression was markedly increased on synovial fluid T lymphocytes of rheumatoid patients relative to peripheral blood lymphocytes from the same individuals. CD44 molecular mass on peripheral blood mononuclear cells was 88 kDa, but that on synovial fluid lymphocytes was only 83 kDa. CD44 expression correlated significantly with expression of activation markers M21C5, M2B3, and the IL-2 receptor. CONCLUSIONS: Alterations in density of expression or of the molecular mass of CD44 could contribute to local tissue injury, either directly by facilitating adhesion, or indirectly through effects on other adhesion molecules.

Arthritis, Rheumatoid↗
PubMed1994

Electron paramagnetic resonance investigations of free radical-induced alterations in neocortical synaptosomal membrane protein infrastructure.

Evidence is presented that free radical stress can directly induce physico-chemical alterations in rodent neocortical synaptosomal membrane proteins. Synaptosomes were prepared from gerbil cortical brain tissue and incubated with 3 mM ascorbate and various concentrations of exogenous Fe2+ for 30-240 min at 37 degrees C. Synaptosomes were then lysed and covalently labeled with the protein thiol-selective spin label MAL-6 (2,2,6,6-tetramethyl-4-maleimidopiperdin-1-oxyl) and subjected to electron paramagnetic resonance (EPR) spectrometry. In separate experiments, synaptosomal membranes were labeled with the thiol-specific spin label MTS ((1-oxyl-2,2,5,5-tetramethyl-pyrroline-3-methyl)-methanethiosulfonate), or the lipid-specific spin probe 5-NS (5-nitroxide stearate). Free radical stress induced by iron/ascorbate treatment has a rigidizing effect on the protein infrastructure of these membranes, as appraised by EPR analysis of membrane protein-bound spin label, but no change was detected in the lipid component of the membrane. These results are discussed with reference to potential oxidative mechanisms in aging and neurological disorders.

Animals↗
PubMed1993

An evaluation of New Jersey's hospital discharge database for surveillance of severe occupational injuries.

Computerized population-based hospital discharge data in New Jersey offer new opportunities for surveillance of serious work-related injuries. This database was evaluated for its potential in identifying selected injuries that occurred at work during 1985 and 1986. Hospital discharge data were compared with data collected by telephone interview of discharged patients. A total of 1,575 unique hospital discharge records for the selected injuries included finger amputation (1,041), thumb amputation (209), crush injury of the lower limb (208), toxic effects of heavy metals (69), and eye burns (48). Of 809 study subjects sent letters, 445 (55%) could be contacted and 289 (36%) were interviewed for the study. Sixty-one percent (175) said their injury was work related. A comparison was made between self-reported injury at work, and the presence of workers' compensation payer codes on the discharge database. The agreement beyond chance (Kappa) was 0.78 (95% CI = 0.67, 0.89). The sensitivity of this indicator of work relatedness was 83%; specificity was 98%. These data suggest that workers' compensation payment on the hospital discharge database may be a good to excellent proxy indicator of the work relatedness of these injuries. However, this proxy indicator will underestimate the number of work-related injuries by about 20%. Only 11% of hospital discharge records had external cause of injury codes (E-codes), which reduces the utility of the database for understanding the causal mechanisms of work-related injuries.

Accidents, Occupational↗
PubMed1993

Hospitalized occupational finger amputations, New Jersey, 1985 and 1986.

About 19,000 finger amputations occur at work each year in the United States. Twenty percent of these injuries are severe enough to require hospitalization. Hospital discharge data from New Jersey (1985, 1986) were used to describe the demographic characteristics of persons with such injuries and to identify potential subjects for telephone interview. A total of 637 persons hospitalized for finger amputations were sent letters asking for their participation. Of 637 persons, 355 (56%) were contacted and 228 (36%) were interviewed, of whom 134 (59%) said their injury occurred at work. The annual rate of finger amputations at work was 9.3 per 100,000 employed persons. The rate was higher for males (14.7) than females (1.9). The age-adjusted rates were higher for Hispanic (52.8) and black (28.9) males than for white males (9.5). Persons working with machines or maintaining them in the manufacturing industry were at highest risk. Unjamming or repairing machinery (e.g., presses, saws, or slicers) while in operation was particularly hazardous. These data can be used to target occupations and industries for specific worksite intervention to prevent finger amputations. One limitation of this study, however, is that hospitalized occupational finger amputations may not be representative of all finger amputations, the majority of which are less severe and do not require hospitalization.

Accidents, Occupational↗
PubMed1993

Interaction of tacrine and velnacrine with neocortical synaptosomal membranes: relevance to Alzheimer's disease.

The acridine-based, potential Alzheimer's disease therapeutic agents, tacrine and velnacrine, were incubated with rat or gerbil neocortical synaptosomal membranes. Electron paramagnetic resonance employing a protein-specific spin label was used to monitor this interaction. Analogous to their effects in erythrocyte membranes [Butterfield and Rangachari (1992) Biochem. Biophys. Res. Commun. 185: 596-603], in the present studies both agents decreased segmental motion of spin labeled synaptosomal membrane proteins, consistent with increased cytoskeletal protein-protein interactions (0.001 < P < 0.005), and tacrine was more potent than velnacrine. These results are discussed with possible relevance to molecular actions of the agents and molecular alterations in Alzheimer's disease.

Alzheimer Disease↗