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Biomedical subjects

J Joseph

Publications and source records attributed to J Joseph.

At least 37 records · Page 2Linked to original sources
PubMed2001

Synthesis and biochemical applications of a solid cyclic nitrone spin trap: a relatively superior trap for detecting superoxide anions and glutathiyl radicals.

A novel cyclic nitrone spin trap, 5-tert-butoxycarbonyl 5-methyl-1-pyrroline N-oxide (BMPO) as a pure white solid has been synthesized for the first time. BMPO offers several advantages over the existing spin traps in the detection and characterization of thiyl radicals, hydroxyl radicals, and superoxide anions in biological systems. The corresponding BMPO adducts exhibit distinct and characteristic electron spin resonance (ESR) spectral patterns. Unlike the 5,5-dimethyl-1-pyrroline N-oxide (DMPO)-derived superoxide adduct, the BMPO superoxide adduct does not non-enzymatically decompose to the BMPO hydroxyl adduct. This feature is clearly perceived as a definite advantage of BMPO in its biological applications. In addition, the ESR spectrum of the BMPO glutathionyl adduct (BMPO/*SG) does not fully overlap with the spectrum of its hydroxyl adduct. This spectral feature is again distinctly different from that of DMPO because the ESR spectral lines of DMPO glutathionyl and hydroxyl radical adducts largely overlap. Finally, the ESR spectra of BMPO-derived adducts exhibit a much higher signal-to-noise ratio in biological systems. These favorable chemical and spectroscopic features make BMPO ideal for the detection of superoxide anions, hydroxyl and thiyl radicals in biochemical oxidation and reduction.

Cyclic N-Oxides↗
PubMed2001

Nitration and oxidation of a hydrophobic tyrosine probe by peroxynitrite in membranes: comparison with nitration and oxidation of tyrosine by peroxynitrite in aqueous solution.

It has been reported that peroxynitrite will initiate both oxidation and nitration of tyrosine, forming dityrosine and nitrotyrosine, respectively. We compared peroxynitrite-dependent oxidation and nitration of a hydrophobic tyrosine analogue in membranes and tyrosine in aqueous solution. Reactions were carried out in the presence of either bolus addition or slow infusion of peroxynitrite, and also using the simultaneous generation of superoxide and nitric oxide. Results indicate that the level of nitration of the hydrophobic tyrosyl probe located in a lipid bilayer was significantly greater than its level of oxidation to the corresponding dimer. During slow infusion of peroxynitrite, the level of nitration of the membrane-incorporated tyrosyl probe was greater than that of tyrosine in aqueous solution. Evidence for hydroxyl radical formation from decomposition of peroxynitrite in a dimethylformamide/water mixture was obtained by electron spin resonance spin trapping. Mechanisms for nitration of the tyrosyl probe in the membrane are discussed. We conclude that nitration but not oxidation of a tyrosyl probe by peroxynitrite is a predominant reaction in the membrane. Thus, the local environment of target tyrosine residues is an important factor governing its propensity to undergo nitration in the presence of peroxynitrite. This work provides a new perspective on selective nitration of membrane-incorporated tyrosine analogues.

Bicarbonates↗
PubMed2001

Imaging of small-scale features on 433 Eros from NEAR: evidence for a complex regolith.

On 25 October 2000, the Near Earth Asteroid Rendevous (NEAR)-Shoemaker spacecraft executed a low-altitude flyover of asteroid 433 Eros, making it possible to image the surface at a resolution of about 1 meter per pixel. The images reveal an evolved surface distinguished by an abundance of ejecta blocks, a dearth of small craters, and smooth material infilling some topographic lows. The subdued appearance of craters of different diameters and the variety of blocks and different degrees of their burial suggest that ejecta from several impact events blanketed the region imaged at closest approach and led to the building up of a substantial and complex regolith consisting of fine materials and abundant meter-sized blocks.

Journal Article↗
PubMed2001

Inhibition of oxidized low-density lipoprotein-induced apoptosis in endothelial cells by nitric oxide. Peroxyl radical scavenging as an antiapoptotic mechanism.

Proatherogenic oxidized low-density lipoprotein (oxLDL) induces endothelial apoptosis. We investigated the anti-apoptotic effects of intracellular and extracellular nitric oxide (*NO) donors, iron chelators, cell-permeable superoxide dismutase (SOD), glutathione peroxidase mimetics, and nitrone spin traps. Peroxynitrite (ONOO-)-modified oxLDL induced endothelial apoptosis was measured by DNA fragmentation, TUNEL assay, and caspase-3 activation. Results indicated the following: (i) the lipid fraction of oxLDL was primarily responsible for endothelial apoptosis. (ii) Endothelial apoptosis was potently inhibited by *NO donors and lipophilic phenolic antioxidants. OxLDL severely depleted Bcl-2 levels in endothelial cells and *NO donors restored Bcl-2 protein in oxLDL-treated cells. (iii) The pretreatment of a lipid fraction derived from oxLDL with sodium borohydride or potassium iodide completely abrogated apoptosis in endothelial cells, suggesting that lipid hydroperoxides induce apoptosis. (iv) Metalloporphyrins dramatically inhibited oxLDL-induced apoptosis in endothelial cells. Neither S-nitrosation of caspase-3 nor induction of Hsp70 appeared to play a significant role in the antiapoptotic mechanism of *NO in oxLDL-induced endothelial apoptosis. We propose that cellular lipid peroxyl radicals or lipid hydroperoxides induce an apoptotic signaling cascade in endothelial cells exposed to oxLDL, and that *NO inhibits apoptosis by scavenging cellular lipid peroxyl radicals.

Animals↗
PubMed2001

Urinary iodine and thyroid status of New Zealand residents.

OBJECTIVES: The aim of this project was to assess the clinical significance of our low iodine excretions in terms of thyroid hormone status and thyroid volume in an adult population in a low soil iodine area of the South Island of New Zealand. DESIGN AND SETTING: Two-hundred and thirty-three residents of Otago, New Zealand collected two 24 h urine samples for assessment of iodine status. Thyroid status was determined from serum total T(4), TSH and thyroglobulin, and thyroid volumes. Relationships between urinary iodide excretion and measures of thyroid status were determined and subjects were allocated to one of three groups according to low, medium and high iodide excretion, for comparison of thyroid hormones and thyroid volumes. RESULTS: Significant correlations were found for relationships between measures of urinary iodide excretion and thyroid volume and thyroglobulin. Multiple regression analysis of data for subjects divided into three groups according to 24 h urinary iodide excretion (<60, 60-90; >90 microg iodide/day) or iodide/creatinine ratio (<40; 40-60; >60 microg/g Cr) showed significant differences in thyroid volume (P=0.029; P=0.035, respectively) and thyroglobulin (P=0.019; P=0.005, respectively) among the groups. CONCLUSIONS: The results of this study confirm the low iodide excretions of Otago residents, and indicate that the fall in iodine status is being reflected in clinical measures of thyroid status, including enlarged thyroid glands and elevated thyroglobulin. Our observations suggest the possible re-emergence of mild iodine deficiency and goitres in New Zealand. This situation is likely to worsen should iodine intakes continue to fall and continued monitoring of the situation is imperative.

Adolescent↗
PubMed2001

Open access follow-up for lung cancer: patient and staff satisfaction.

The majority of patients with lung cancer have incurable disease from presentation and a survival measured in months. Treatments offered to these patients are aimed at the palliation of symptoms with either radiotherapy or chemotherapy, or with supportive measures. It has been traditional to offer regular outpatient follow-up after initial palliative treatment. Further treatment options, which may be limited, are usually reserved for the recurrence of troublesome symptoms. A pilot 'open access' lung cancer clinic has been set up. Rather than have regular follow-up at the hospital, patients who have completed initial palliative treatments are discharged to the community with follow-up by their general practitioner and Macmillan nurse. Review at the open access clinic can be arranged at short notice if requested by the patient, carers, general practitioner or Macmillan nurse. The outcomes and level of satisfaction of patients, their relatives and staff to this method of follow-up were found to be positive. Open access follow-up may be useful for many patients after the completion of initial palliative treatment.

Attitude of Health Personnel↗
PubMed2001

Pediatric heart transplantation: improving results in high-risk patients.

OBJECTIVES: Our institutional experience with 73 pediatric patients undergoing cardiac transplantation between January 1, 1990, and December 31, 1999, was reviewed to determine the impact of unconventional donor and recipient management protocols implemented to extend the availability of this therapy. METHODS AND RESULTS: The introduction of donor blood cardioplegic solution with added insulin was associated with a significant improvement in patient and graft survival (hazard ratio [Cox] = 0.25, P =.08), despite significantly longer ischemic times with this protocol compared with the use of crystalloid-based donor procurement techniques (P <.01). Eleven patients underwent intentional transplantation of ABO-incompatible donor hearts with the aid of a protocol of plasma exchange on bypass. In this subgroup, there were 2 early deaths caused by nonspecific graft failure (n = 1) and respiratory complications with mild vascular rejection (n = 1), and there was 1 late death caused by lymphoma. ABO-incompatible transplantation was not a risk factor for death by multivariate analysis. The postoperative course in these patients suggests minimal reactivity directed against incompatible grafts on the basis of low anti-donor blood group antibody production, in association with a favorable rejection profile. Ten of 13 patients requiring preoperative support with an extracorporeal membrane oxygenator survived transplantation; there were 3 additional late deaths in this subgroup (hazard ratio = 2.88, P =.05). CONCLUSIONS: The results with pediatric cardiac transplantation continue to improve as a result of changes in both surgical and medical protocols permitting successful treatment of patients conventionally considered at high risk or unsuitable for transplantation.

ABO Blood-Group System↗
PubMed2001

Is the pleural fluid transudate or exudate? A revisit of the diagnostic criteria.

BACKGROUND: Pleural effusions are classified into transudates and exudates based on criteria developed in the 1970s. However, their accuracy has not been evaluated. We compared the performance of the pleural fluid absolute lactic dehydrogenase level (FLDH), fluid to serum ratio of LDH (LDHR), and fluid to serum ratio of total protein (TPR). TPR has been used instead of the absolute value of fluid protein based on the observation that fluid protein is influenced by changes in the serum protein concentration. However, the rationale for using LDHR remains unexplored. METHODS: Of 212 consecutive patients with pleural effusions, four with multiple causes and eight with an uncertain diagnosis were excluded. ROC curves were generated using sensitivity and 1-specificity values for TPR, FLDH, and LDHR and positive likelihood ratios (LR+ve) were computed using the optimum cut off values. The correlation between pleural fluid and serum concentrations of total protein and LDH was also estimated. RESULTS: Of 200 effusions studied, 156 were exudates and 44 were transudates. The optimum cut off levels were: FLDH 163 IU/l, TPR 0.5, LDHR 0.6, and the FLDH-TPR combination 163 and 0.4, respectively. The area under the curve (AUC) with 95% confidence interval (CI) was: 0.89 (0.86 to 0.96) for FLDH, 0.86 (0.80 to 0.91) for TPR, 0.82 (0.77 to 0.89) for LDHR, and 0.90 (0.86 to 95) for FLDH-TPR. A significant correlation was observed between serum and pleural fluid protein levels in transudates and exudates (r=0.5 and 0.6, respectively), but the correlation between serum and pleural fluid LDH levels was insignificant. CONCLUSION: FLDH is the most accurate marker for the diagnostic separation of transudates and exudates and LDHR has no role in this process. Combining TPR with FLDH appears to improve the diagnostic accuracy slightly.

Adolescent↗
PubMed2001

Cytochrome-c detection: a diagnostic marker for myocardial infarction.

Following a myocardial infarction (MI) cells die or are damaged and their contents leak into the blood circulation, resulting in elevated serum levels of various enzymes, proteins, and organic molecules. Over the past few decades, it has become standard practice to employ the detection of these elevated substances as markers for the confirmation of MIs and to monitor MI patients' response to treatment. Although it has previously been shown that cytochrome-c, a small respiratory protein, is among those elevated, the lack of a suitable detection system has prevented its routine use in the diagnosis of MIs. We present a preliminary study in which chemiluminescence was employed to detect elevated levels of cytochrome-c in the serum of MI patients. The technique, which is specific for c-type proteins, is approx 30 times more sensitive than the traditional Coomassie blue stain and can detect as little as 0.03 microg of protein. It also has potential for diagnostic use in other diseases that are characterized by mitochondrial damage.

Biomarkers↗
PubMed2001

Influence of photoperiod, laboratory caging and aging on plasma lipid response to an atherogenic diet among F1B hamsters.

The effects and interactions of photoperiod, animal caging, aging and diet on plasma lipid levels in male F1B hamsters were examined in the current study. Sixteen young and sixteen old animals were housed one or four per cage. Eight young animals from each housing group were placed in an animal room with either 12/12 h (PT-12) or 10/14 h (PT-10) light/dark cycle while the sixteen old animals were maintained under a PT-12 light cycle. Plasma cholesterol and triglyceride concentrations were determined in all animals after a 2-week period of acclimation on chow diet and following 4-week intervention on atherogenic diet. Baseline total cholesterol (TC) levels were 131+/-25 mg/dl and 142+/-39 mg/dl for young and old animals, respectively, while baseline triglyceride (Tg) levels were 202+/-48 mg/dl and 160+/-37 mg/dl respectively for the same animals. Following 4-weeks on an atherogenic diet, single-caged PT 12 animals had elevated but significantly lower TC levels than group-caged animals (161+/-30 mg/dl and 240 +/-58 mg/dl, respectively) while single and group housed PT10 animals had TC levels of 296+/-75 mg/dl and 351+/-124 mg/dl, respectively. Similarly, plasma Tg levels rose to 330+/-100 mg/dl and 486+/-200 mg/dl in single and group housed PT12 animals (respectively) and to 668+/-270 mg/dl and 545+/-199 mg/dl in single and group housed PT10 animals (respectively). No significant changes related to atherogenic diet were observed in plasma TC or Tg levels in the older animals. Although caging conditions influence the cholesterol and triglyceride response to the atherogenic diet (p<.05), light cycle photoperiod seems to exert a greater effect (p<.005). In conclusion, photoperiod length dramatically affects diet-induced plasma lipid concentrations in young male F1B hamsters, and thus needs be considered in experimental designs of animal-housed lipid research.

Aging↗
PubMed2001

Separated twins and the genetics of personality differences: a critique.

This article discusses studies of separated twins, with special emphasis on the Minnesota Study of Twins Reared Apart (MISTRA), to determine whether they support the existence of an important genetic component in behavioral and personality differences. The methods and conclusions of the MISTRA team are discussed in the context of earlier studies of separated identical twins. I argue that volunteer-based studies are biased toward greater twin similarity. In addition, the MISTRA research team did not publish or share raw data and case history information. Reared-together and reared-apart monozygotic twins share important environmental similarities not controlled for by comparing personality correlations. I propose an alternative control group consisting of biologically unrelated pairs of strangers matched on all environmental factors common to pairs of separated monozygotic twins. I conclude that the evidence from studies of twins reared apart does not support the role of genetic factors in personality and behavioral differences.

Behavior↗
PubMed2001

Don Jackson's "A critique of the literature on the genetics of schizophrenia": a reappraisal after 40 years.

In 1960, Don Jackson published "A Critique of the Literature on the Genetics of Schizophrenia." Jackson's critique nearly relegated the classical twin method to obscurity as being hopelessly confounded by environmental factors. Jackson noted several trends in the schizophrenia twin data that were difficult to explain on genetic grounds. In fact, none of Jackson's 12 major points, examined in this article, have been satisfactorily answered by proponents of the twin method. The evidence in support of Jackson's most controversial claim-that the psychology of twinship itself might lead to a greater rate of schizophrenia among twins when compared with the single-born population--is inconclusive. However, although several leading twin researchers have dismissed Jackson's entire thesis on the basis of the inconclusiveness of this one claim, this idea was not central to Jackson's basic argument. The research undertaken for this article appears to confirm the validity of the most important points of Jackson's analysis and that therefore the classical twin method is of doubtful value as an indicator of genetic influences on schizophrenia and other diagnoses or psychological trait differences. Jackson's article demonstrated the implausibility of what came to be known as the MZ/DZ "equal environment assumption" of the twin method, implying that the twin method records nothing more than environmental differences between monozygotic and dizygotic twins.

Environment↗
PubMed2001

Volatile essential oil constituents of Alpinia smithiae (Zingiberaceae).

The composition of leaf and rhizome essential oils of Alpinia smithiae that grow wild in the Western Ghats of Kerala (South India) was analysed by gas chromatography. The major components were beta-caryophyllene, sabinene, myrcene and 1,8-cineole in both samples, but variation in the yield of oil as well as the major components between the two plant parts was observed.

Chromatography, Gas↗
PubMed2000

Doxorubicin-induced apoptosis in endothelial cells and cardiomyocytes is ameliorated by nitrone spin traps and ebselen. Role of reactive oxygen and nitrogen species.

Doxorubicin (DOX) is a broad spectrum anthracycline antibiotic used to treat a variety of cancers. Redox activation of DOX to form reactive oxygen species has been implicated in DOX-induced cardiotoxicity. In this work we investigated DOX-induced apoptosis in cultured bovine aortic endothelial cells and cardiomyocytes isolated from adult rat heart. Exposure of bovine aortic endothelial cells or myocytes to submicromolar levels of DOX induced significant apoptosis as measured by DNA fragmentation and terminal deoxynucleotidyltransferase-mediated nick-end labeling assays. Pretreatment of cells with 100 microm nitrone spin traps, N-tert-butyl-alpha-phenylnitrone (PBN) or alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (POBN) dramatically inhibited DOX-induced apoptosis. Ebselen (20-50 microm), a glutathione peroxidase mimetic, also significantly inhibited apoptosis. DOX (0.5-1 microm) inactivated mitochondrial complex I by a superoxide-dependent mechanism. PBN (100 microm), POBN (100 microm), and ebselen (50 microm) restored complex I activity. These compounds also inhibited DOX-induced caspase-3 activation and cytochrome c release. PBN and ebselen also restored glutathione levels in DOX-treated cells. We conclude that nitrone spin traps and ebselen inhibit the DOX-induced apoptotic signaling mechanism and that this antiapoptotic mechanism may be linked in part to the inhibition in formation or scavenging of hydrogen peroxide. Therapeutic strategies to mitigate DOX cardiotoxicity should be reexamined in light of these emerging antiapoptotic mechanisms of antioxidants.

Animals↗