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Biomedical subjects

A C Carr

Publications and source records attributed to A C Carr.

At least 19 recordsLinked to original sources
PubMed1999

Increased prevalence of antithyroid antibodies identified in women with recurrent pregnancy loss but not in women undergoing assisted reproduction.

OBJECTIVE: To assess the prevalence of antibodies to thyroglobulin and thyroid peroxidase (or microsomal) in women with recurrent pregnancy loss and women undergoing assisted reproductive techniques (ART) compared with healthy controls. DESIGN: Retrospective, two-centered study. SETTING: University-affiliated private patient centers. PATIENT(S): Included were 700 women with a history of two or more consecutive pregnancy losses, 688 women with a history of infertility who were undergoing ART, and 200 healthy, reproductive-aged female controls. INTERVENTION(S): Blood was collected before ART cycles, frozen, and assayed. MAIN OUTCOME MEASURE(S): Standardized ELISAs were used to measure antithyroid antibodies and TSH levels. Statistical analysis was performed with use of the two-tailed Fisher's exact test. RESULT(S): Antithyroid antibodies were identified in 29 of 200 (14.5%) of controls and 158 of 700 (22.5%) of women with recurrent pregnancy loss and 132 of 688 (19.2%) of women undergoing ART. Less than 20% of the women with antithyroid antibodies were clinically hypothyroid. CONCLUSION(S): Antithyroid antibodies are identified more frequently in women with recurrent pregnancy loss than in controls but not in women undergoing ART. These autoantibodies may be markers of autoimmune activation and have been associated with an increased risk of pregnancy loss and postpartum thyroid disease.

Abortion, Habitual↗
PubMed1998

Differential reactivities of hypochlorous and hypobromous acids with purified Escherichia coli phospholipid: formation of haloamines and halohydrins.

Hypochlorous (HOCl) and hypobromous (HOBr) acids are strong oxidants derived from myeloperoxidase and eosinophil peroxidase, the major antimicrobial enzymes of neutrophils and eosinophils, respectively. These oxidants are highly reactive with a wide range of biomolecules. At physiological pH, both HOCl and HOBr react readily with amines to form haloamines and with the unsaturated bonds of fatty acids to form halohydrins. We have investigated which of these reactions occur with phosphatidylethanolamine (PE), the predominant phospholipid of Escherichia coli. The formation of haloamines was determined by TLC and colorimetrically and the formation of halohydrins was determined by TLC and GC-MS. With HOCl, chloramines were much the preferred product and chlorohydrins were formed in substantial amounts only when HOCl was in excess of the amount required to convert the amine to the dichloramine. With HOBr at all concentrations, bromamines and bromohydrins were formed concurrently, indicating a greater relative reactivity with unsaturated fatty acids than with HOCl. The bromamine derivatives of PE, and other primary amines, were found to be more reactive than the equivalent chloramines, and were able to brominate the unsaturated bonds of fatty acids. Bromohydrins (formed directly or through the action of bromamines) may, therefore, be suitable biomarkers for the production of HOBr in vivo.

Alcohols↗
PubMed1998

Comparison of human red cell lysis by hypochlorous and hypobromous acids: insights into the mechanism of lysis.

Human red blood cells are lysed by the neutrophil-derived oxidant hypochlorous acid (HOCl), although the mechanism of lysis is unknown. Hypobromous acid (HOBr), a similarly reactive oxidant, lysed red cells approx. 10-fold faster than HOCl. Therefore we compared the effects of these oxidants on thiols, membrane lipids and proteins to determine which reactions are associated with lysis. There was no difference in the loss of reduced glutathione or membrane thiols with either oxidant, but HOBr reacted more readily with membrane lipids and proteins. Bromohydrin derivatives of phospholipids and cholesterol were seen at approx. one-tenth the level of oxidant than chlorohydrins were. However, these products were detected only with high concentrations of HOCl or HOBr, which caused instant haemolysis. Membrane protein modification occurred at much lower doses of oxidant and was more closely correlated with lysis. SDS/PAGE analysis showed that band 3, the anion transport protein, was lost at the lowest dose of HOBr and at the higher concentrations of HOCl. Labelling the red cells with eosin 5-maleimide, a fluorescent label for band 3, suggested possible clustering of this protein in oxidant-exposed cells. There was also irreversible cross-linking of all the major membrane proteins; this reaction occurred more readily with HOBr. The results indicate that membrane protein modification is the reaction responsible for HOCl-mediated lysis. These effects, and particularly cross-link formation, might result in clustering of band 3 and other membrane and cytoskeletal proteins to form haemolytic pores.

Anion Exchange Protein 1, Erythrocyte↗
PubMed1997

Oxidation of neutrophil glutathione and protein thiols by myeloperoxidase-derived hypochlorous acid.

Neutrophils, when stimulated, generate reactive oxygen species including myeloperoxidase-derived HOCl. There is an associated decrease in reduced glutathione (GSH) concentration. We have shown that neutrophil GSH levels decrease on exposure to reagent HOCl, whereas the equivalent concentration of H2O2 had no effect. GSH loss occurred without cell lysis, was not reversible, and was accompanied by the loss of an equivalent proportion of the total protein thiols. No glutathione disulphide was formed. Studies with 35S-labelled cells indicated that much of the GSH lost was accounted for by mixed disulphides with protein and a product that co-migrated on HPLC with a novel compound formed in the reaction of HOCl and pure GSH. The properties of this compound are consistent with an intramolecular sulphonamide. Neutrophils stimulated with PMA lost 30-40% of their GSH and a similar proportion of protein thiols. Little glutathione disulphide was formed and the products were the same as seen with HOCl-treated cells. From the results and studies with inhibitors and scavengers, we conclude that HOCl was responsible for the GSH loss. Propargylglycine and buthionine sulphoximine, inhibitors of glutathione synthesis, enhanced GSH loss, but their effects were due to the production of long-lived chloramines that oxidized GSH with greater efficiency than HOCl, rather than to the inhibition of GSH synthesis. The lack of thiol selectivity by HOCl and irreversibility of oxidation means that GSH will provide limited antioxidant protection for thiol enzymes in stimulated neutrophils.

Alkynes↗
PubMed1997

Nuclear magnetic resonance characterization of 6 alpha-chloro-5 beta-cholestane-3 beta,5-diol formed from the reaction of hypochlorous acid with cholesterol.

Hypochlorous acid generated by neutrophil myeloperoxidase has been shown to convert cholesterol into three different chlorohydrin isomers which previously had not been fully characterized. We have reacted hypochlorous acid with cholesterol/1,2-dipalmitoyl phosphatidylcholine liposomes to give these three major products and established that they are 6 beta-chloro-5 alpha-cholestane-3 beta,5-diol (chlorohydrin 1), 5 alpha-chloro-6 beta-cholestane-3,6-diol (chlorohydrin 2) and 6 alpha-chloro-5 beta-cholestane-3 beta,5-diol (chlorohydrin 3). These products were separated by thin-layer chromatography and fully characterized by 1H, 13C, attached proton test, doublequantum correlation spectroscopy, total correlation spectroscopy, heteronuclear multiple bond correlation and heteronuclear multiple quantum coherence nuclear magnetic resonance spectroscopy.

Cholestanols↗
PubMed1996

Chlorination of cholesterol in cell membranes by hypochlorous acid.

Neutrophils and monocytes produce the highly cytotoxic hypochlorous acid (HOCl) via the myeloperoxidase (MPO)-catalyzed reaction of H2O2 with Cl-. We have investigated the reaction of reagent and MPO-derived HOCl with cholesterol in a purified liposome system, as well as progressively more complex biological systems. The products were identified by thin-layer chromatography (TLC) and characterized by mass spectrometry (MS). TLC of the HOCl-treated samples gave four major cholesterol products with color development typical of oxysterols. Two of the products coeluted with authentic alpha- and beta-chlorohydrin standards. As was the case with the standards, they were readily converted into their respective epoxides during analysis by MS. Gas chromatography-mass spectrometry analysis of the other major product (band 3) gave peaks consistent with epoxides as well as a lateeluting peak with a distinct mass spectrum. Electrospray MS of this product confirmed its identity as a chlorohydrin based on the presence of the predicted molecular ion and 3:1 Cl isotope ratios. Lipids extracted from red cells and isolated red cell membranes were exposed to HOCl and gave identical products to the purified cholesterol liposome system as determined by TLC and MS. Higher concentrations of HOCl were required due to competition by other unsaturated lipids and protein molecules. When intact red cells, neutrophils, and MCF7 mammary carcinoma cells were exposed to HOCl, cholesterol chlorohydrins were formed, as detected by TLC. The formation of cholesterol chlorohydrins could be potentially disruptive to cell membranes and result in cell lysis and death. They could also be potential biomarkers for oxidative damage associated with neutrophil/monocyte activation.

Cell Membrane↗
PubMed1996

Peroxidase-mediated bromination of unsaturated fatty acids to form bromohydrins.

Eosinophil peroxidase and myeloperoxidase (MPO) catalyze the oxidation of bromide by hydrogen peroxide to produce hypobromous acid (HOBr). Hypochlorous acid, which is also generated by MPO, reacts with unsaturated fatty acids to form chlorohydrins. In this study the equivalent reaction of HOBr, produced from MPO, bromide, and hydrogen peroxide, with oleic (18:1), linoleic (18:2), and arachidonic (20:4) acids has been investigated. Thin-layer chromatography detected one major product of higher polarity than the unmodified fatty acids and additional more polar products with the polyunsaturated fatty acids. Similar results were observed with N-bromosuccinimide-derived HOBr. Gas chromatography-mass spectrometry (GC-MS) and electrospray MS identified the major products of 18:1 as the isomeric 9,10-bromohydrins based on retention time and mass spectrometric isotope and fragmentation patterns. The products of 18:2 and 20:4 were too unstable for analysis by GC-MS. Electrospray MS identified the mono- and bisbromohydrins formed from 18:2 and 20:4 based on mass/charge ratios of the molecular ions and the presence of bromine isotope patterns. Other oxidation products not containing bromine, such as dihydroxy derivatives, were detected as well. Fatty acid bromohydrins could contribute to the antimicrobial activity and inflammatory tissue damage by eosinophils and neutrophils, and could potentially be useful specific markers for HOBr production in vivo.

Alcohols↗
PubMed1995

Vitamin A and E status in very low birth weight infants: development of an improved parenteral delivery system.

Plasma vitamin A and E levels were inadequate in very low birth weight infants receiving a continuous infusion of a parenteral multivitamin preparation, 1.5 ml/kg per day, in dextrose-amino acid solution. A new delivery system using 2 ml/kg per day, infused for 6 hours from the first day of life, avoided loss during infusion and significantly improved plasma vitamin A and E levels during the first 28 days of life in very low birth weight infants.

Avitaminosis↗
PubMed1994

Assays using horseradish peroxidase and phenolic substrates require superoxide dismutase for accurate determination of hydrogen peroxide production by neutrophils.

We used horseradish peroxidase and either scopoletin, homovanillic acid, or phenol red to measure hydrogen peroxide generated by human neutrophils. With these assays, superoxide dismutase significantly increased the amount of hydrogen peroxide detected. In contrast, it had no effect when the accumulation of hydrogen peroxide was measured with a hydrogen peroxide electrode. We propose that superoxide interferes with horseradish peroxidase-dependent assays so that hydrogen peroxide is underestimated. Thus, when using these assays, superoxide dismutase must be added to neutrophils to ensure that all the hydrogen peroxide they produce is detected.

Horseradish Peroxidase↗
PubMed1993

Myeloperoxidase-dependent loss of malondialdehyde: a limitation for detecting neutrophil-mediated lipid peroxidation.

Lipid peroxidation is commonly measured using the thiobarbituric acid (TBA) assay. We have examined how this assay is affected by hypochlorite, which is generated by the neutrophil enzyme myeloperoxidase. The TBA reactivity of phospholipid liposomes that had been partially peroxidized with iron/ascorbate was destroyed by low concentrations of sodium hypochlorite. Since most of the TBA reactivity in peroxidized liposomes is due to malondialdehyde, its reactivity was investigated. Addition of sodium hypochlorite destroyed the uv absorbance of malondialdehyde with a 2:1 stoichiometry and eliminated its TBA reactivity. The TBA reactivity of malondialdehyde and peroxidized liposomes was also lost after treatment with myeloperoxidase. The reaction with myeloperoxidase required chloride and was inhibited by catalase and methionine, indicating the involvement of hypochlorite. Neutrophils stimulated with phorbol myristate acetate or N-formyl-methionyl-leucyl-phenylalanine destroyed the TBA reactivity of malondialdehyde and peroxidized liposomes by a hypochlorite-dependent mechanism. The ability of hypochlorite to break down malondialdehyde explains why lipid peroxidation by stimulated neutrophils, as measured with TBA, is apparently inhibited by myeloperoxidase. Myeloperoxidase may not, however, inhibit the peroxidation process. The TBA assay and other assays of malondialdehyde may be of limited value, therefore, for assessing lipid peroxidation in systems where neutrophils or myeloperoxidase are involved.

Chlorides↗
PubMed1991

Treatment-resistant depression: a survey of practice habits of Canadian psychiatrists.

Treatment-resistant depression is a fascinating yet poorly defined condition. The various management strategies in use are a source of controversy. The objective of this survey was to determine how Canadian psychiatrists treat patients with "intractable depression." This information may be used to plan future research into the management of treatment-resistant depression. It may also provide information about the practices of Canadian psychiatrists and help direct residency training. Confidential questionnaires were mailed to all psychiatrists residing in Canada registered with the Canadian Psychiatric Association. Respondents indicated that 12.4% of their depressed patients were "resistant to treatment." Respondents were asked to rank a list of treatment choices in the order they would use them to treat patients with treatment-resistant depression. Ninety-five point eight percent of respondents used tricyclics as the first treatment of choice. Almost equal portions of respondents chose a second tricyclic, a monoamine oxidase inhibitor (MAOI) or a combination of lithium and tricyclics as their treatment of second choice.

Antidepressive Agents↗
PubMed1990

Assessment of adult relatedness: a review of empirical findings from object relations and attachment theories.

Assessment techniques designed to measure adult behavior and mental representation that emphasize relatedness constructs are reviewed. These measures grow out of two traditions, object relations and attachment theories. Although these two paradigms are fairly well elucidated theoretically, the relevant assessment literature is only more recently expanding, especially that focusing directly on adult attachment as opposed to childhood attachment. In addition to a presentation of various projective and objective measures, this review highlights the clinical and research implications for integration of these two paradigms around the cognitive, affective, and behavioral vicissitudes of adult relatedness.

Adult↗
PubMed1989

Reaction time impairment in schizophrenia and affective illness: the role of attention.

A young but chronic group of schizophrenic and affective disorders patients was tested for simple reaction time (RT) and RT while engaged in a concurrent task. The affective disorders patients were subdivided by the presence of psychotic features. The results show that extreme slowing of RT is due to psychoticism and is not characteristic of nonpsychotic affective illness. Extreme intrasubject variability, however, was specific to schizophrenia, and may be a trait marker of the disorder.

Adult↗
PubMed1988

Computer-supervised exposure treatment for phobias.

Twenty phobic outpatients were treated by 9 weekly "interviews" at the console of a desk computer. Using a conversational style and multiple choice questions, the computer assessed the symptoms and agreed a hierarchy of self-exposure tasks. Each week the patient was given a diary sheet of tasks to practise daily. At his next visit his progress and motivation were assessed, and if he was succeeding he was encouraged to accept progressively more difficult tasks. This group was compared with a group of 20 patients (matched for age, sex and type of phobia) treated conventionally by a therapist in the preceding year. Progress was measured on standardized scales (both self- and clinician-rated). The two groups showed significant improvement on all the scales, and 75-80% of each group were much improved (scores reduced by 50%). The therapist treated group tended to be more severely ill at entry and to show greater improvement during treatment. Improvement was maintained at 6 month follow-up in both groups.

Adult↗
PubMed1988

Therapist contact and outcome of self-exposure treatment for phobias. A controlled study.

Eighty-four chronic phobic patients were randomly assigned to self-exposure in vivo instructed by either a psychiatrist, a computer or a book; mean therapy time per patient was respectively 3.1, 3.2 and 0 hours. Seventy-one patients completed treatment. All three groups improved substantially and similarly to 6 months follow-up, with no significant difference between them; self-exposure treatment was effective even without therapist contact. Among the three groups, initial expectation of help and positive attitude to the psychiatrist were equally high and related to subsequent rating of help received. All three groups rated the psychiatrist as more tolerant, reliable, and understanding than the computer or book, but these attitudes did not relate to outcome, were initially similar among all three groups, and changed minimally at 6 months follow-up.

Adolescent↗
PubMed1986

Automated cognitive assessment of elderly patients: a comparison of two types of response device.

Groups of 14 cognitively impaired elderly people were tested on two automated cognitive tests on several occasions. Patients registered their responses using either a touch-sensitive screen or a board with illuminated response buttons. The results indicate that the touch-sensitive screen is probably a more suitable response device than the button-board. Suggestions that it would prove disadvantageous to elderly patients were not supported, and its continued use is recommended.

Aged↗