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Biomedical subjects

M R Boyd

Publications and source records attributed to M R Boyd.

At least 37 records · Page 2Linked to original sources
PubMed2000

Human brain thioltransferase: constitutive expression and localization by fluorescence in situ hybridization.

Thioltransferase (glutaredoxin) is a member of the family of thiol-disulfide oxido-reductases that maintain the sulfhydryl homeostasis in cells by catalyzing thiol-disulfide interchange reactions. One of the major consequences of oxidative stress in brain is formation of protein-glutathione mixed disulfide (through oxidation of protein thiols) which can be reversed by thioltransferase during recovery of brain from oxidative stress. Here we have visualized the location of thioltransferase in brain regions from seven human tissues obtained at autopsy. Constitutively expressed thioltransferase activity was detectable in all human brains examined although inter-individual variations were seen. The enzyme activity was significantly higher in hippocampus and cerebellum as compared to other regions. Constitutive expression of thioltransferase mRNA was detectable by Northern blot analysis. Localization of thioltransferase mRNA by fluorescence in situ hybridization revealed its presence predominantly in neurons in the cerebral cortex, Purkinje and granule cell layers of the cerebellum, granule cell layer of the dentate gyrus and in the pyramidal neurons of CA1, CA2 and CA3 subfields of hippocampus. These discrete neuronal concentrations of thioltransferase would be consistent with an essential role in modulating recovery of protein thiols from mixed disulfides formed during oxidative stress.

Adult↗
PubMed2000

Antineoplastic agents. 443. Synthesis of the cancer cell growth inhibitor hydroxyphenstatin and its sodium diphosphate prodrug.

A structure-activity relationship (SAR) study of the South African willow tree (Combretum caffrum) antineoplastic constituent combretastatin A-4 (3b) led to the discovery of a potent cancer cell growth inhibitor designated phenstatin (5a). This benzophenone derivative of combretastatin A-4 showed remarkable antineoplastic activity, and the benzophenone derivative of combretastatin A-1 was therefore synthesized. The benzophenone, designated hydroxyphenstatin (6a), was synthesized by coupling of a protected bromobenzene and a benzaldehyde to give the benzhydrol with subsequent oxidation to the ketone. Hydroxyphenstatin was converted to the sodium phosphate prodrug (6e) by a dibenzyl phosphite phosphorylation and subsequent benzyl cleavage (6a --> 6d --> 6e). While hydroxyphenstatin (6a) was a potent inhibitor of tubulin polymerization with activity comparable to that of combretastatin A-1 (3a), the phosphorylated derivative (6e) was inactive.

Animals↗
PubMed2000

Multiple forms of cytochrome P450 and associated monooxygenase activities in human brain mitochondria.

We have investigated cytochrome P450 (P450) and associated monooxygenase activities in human brain mitochondria isolated from eight regions of four human brain samples obtained at autopsy. P450-associated monooxygenase activities including aminopyrine N-demethylase (APD), 7-ethoxycoumarin O-deethylase (ECD), p-nitrophenol hydroxylase (PNPH), and N-nitrosodimethylamine N-demethylase (ND-MAD) were detectable in the mitochondria from human brain regions. Immunoblot experiments using antisera to purified rat liver microsomal P450, namely P4502B1/2, P4501A1/2, and P4502E1, revealed immunoreactive bands in isolated mitochondria from different regions of the human brain. The antibody to P4502B1/2 and P4501A1/2 inhibited the human brain mitochondrial APD and ECD activities, respectively. The addition of antiserum to microsomal NADPH cytochrome P450 reductase did not affect the mitochondrial P450-associated monooxygenase activities, although it completely inhibited the corresponding activities in brain microsomes. Overall, the present study demonstrates, in human brain mitochondria, the presence of multiple forms of P450 belonging to the 1A, 2B, and 2E subfamilies that are involved in xenobiotic metabolism.

Adult↗
PubMed2000

Cycloviolins A-D, anti-HIV macrocyclic peptides from Leonia cymosa.

Four novel anti-HIV macrocyclic peptides containing 28-31 amino acid residues, named cycloviolins A-D, have been isolated from the hitherto unstudied tropical plant Leonia cymosa. Their primary structure, including amino acid composition and sequence, was determined by a combination of MALDI-TOF and FAB MS and by enzymatic digestion of reduced derivatives, followed by Edman degradation and mass analyses. All of the cycloviolins contain six cysteines, which are present as three intramolecular disulfide bridges. Intriguingly, cycloviolins A-D showed high degrees of sequence homology to the known cyclopsychotride A and circulins A and B from the Rubiaceae family but much less homology to the varv peptides from Viola, a member of the same family (Violaceae).

Amino Acid Sequence↗
PubMed2000

Cytochrome P4502E (CYP2E) in brain: constitutive expression, induction by ethanol and localization by fluorescence in situ hybridization.

Cytochrome P4502E (P4502E), the major ethanol-inducible P450 metabolizes ethanol to acetaldehyde and bioactivates procarcinogens to ultimate carcinogens. Metabolism of ethanol to acetaldehyde in the brain could be deleterious since it can react with cytoskeletal proteins, forming adducts. In the present study, rats were administered ethanol chronically to evaluate its effect on chlorzoxazone hydroxylation in rat brain regions. Chlorzoxazone hydroxylation in brains from the treated rats was induced in hippocampus and cortex, downregulated in brainstem, and unchanged in cerebellum, striatum, and thalamus. The presence of functionally active P4502E was also seen in human brain regions obtained at autopsy from traffic accident victims. Northern blot analysis of rat and human brain poly(A)(+) RNA hybridized with cDNA to rat CYP2E1 revealed the constitutive presence of a corresponding transcript in rat and human brain. Localization of CYP2E by fluorescence in situ hybridization demonstrated the constitutive expression of CYP2E preferentially in the neuronal cells in rat and human brain. CYP2E expression was seen in neurons within the cerebral cortex, Purkinje and granule cell layers of cerebellum, granule cell layer of dentate gyrus, and pyramidal neurons of CA1, CA2, and CA3 subfields of hippocampus in both rat and human brain. The present studies demonstrate constitutive expression of P4502E1 in brain, its differential induction in rat brain regions by chronic ethanol treatment, and its topographic distribution in rat and human brain.

Adult↗
PubMed2000

Cytotoxic clerodane diterpene esters from Laetia corymbulosa.

Three cytotoxic clerodane diterpene esters, corymbulosins A-C, were isolated from an organic extract of the fruit of Laetia corymbulosa (Flacourtiaceae) from Peru. The structures were determined by spectroscopic methods as clerodane diterpenes unsaturated at C-3, C-13(16) and C-14. Corymbulosin A was esterified at C-2 with a decadienoate moiety, while corymbulosins B and C were C-2 epimers esterified at C-6 with a decanoate moiety.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Predicting substance abuse and comorbidity in rural women.

Substance abuse in women is underdiagnosed. Moreover, women are more likely to have a primary comorbid psychiatric disorder that complicates diagnosis and treatment. The purpose of this study was to identify risk factors that would predict substance abuse and primary comorbid psychiatric disorders in rural women. Discriminant function analysis identified 2 factors, alcohol beliefs and threats of minor violence, which correctly identified substance abusing women from nonsubstance abusing women, and women with nonsubstance use psychiatric disorders from those with no psychiatric disorder. These 2 functions correctly classified 69% of women in the study. Psychiatric diagnoses and nursing implications are discussed.

Adolescent↗
PubMed2000

Isolation and characterization of Myrianthus holstii lectin, a potent HIV-1 inhibitory protein from the plant Myrianthus holstii(1).

Aqueous extracts from the African plant Myrianthus holstii potently inhibited the infection of the T-lymphoblastoid cell line, CEM-SS, by human immunodeficiency virus-1(RF) (HIV-1(RF)). The active constituent, M. holstii lectin (MHL), was purified by LH-20 column chromatography and reversed phase HPLC. MHL, a 9284-Da cysteine-rich protein, was characterized by amino acid analysis, N-terminal sequencing, ESIMS, and matrix-assisted laser-desorption ionization-time-of-flight mass spectrometry. Pure MHL had anti-HIV activity, with an EC(50) value of 150 nM. Delaying the addition of MHL for up to 8 h after initial exposure of CEM-SS cells to virus did not result in loss of the antiviral activity; however, if addition of the compound was delayed for 16 h or more, there was a marked decrease in the antiviral activity. MHL bound to a virus-free, soluble form of the viral envelope protein gp120 but did not inhibit the subsequent binding to a cell-free, soluble form of the cellular receptor CD4.

Amino Acid Sequence↗
PubMed2000

Haligramides A and B, two new cytotoxic hexapeptides from the marine sponge Haliclona nigra.

Bioassay-guided fractionation of a cytotoxic aqueous extract of the sponge Haliclona nigra provided two new cyclic hexapeptides, haligramides A (1) and B (2), in addition to the known peptide, waiakeamide (3). The structures of peptides 1 and 2 were elucidated by extensive NMR analyses and by comparison of their spectral data with those of waiakeamide (3). The identity of haligramide A (1) was confirmed by its oxidative conversion to waiakeamide (3). Further structural confirmation was provided by oxidation of peptides 1, 2, and 3 to the common bis-sulfone derivative 4.

Animals↗
PubMed2000

Stolonic acids A and B, new cytotoxic cyclic peroxides from an Indian Ocean ascidian Stolonica species.

Two new 3,6-epidioxy-7,10-tetrahydrofurano C(26) unsaturated fatty acids, stolonic acids A (1) and B (2), were isolated from a previously undescribed ascidian species, Stolonica sp. collected off the Maldive Islands in the Indian Ocean. The structures and relative stereochemistry of 1 and 2 were determined using conventional spectroscopic methods. Both compounds exhibited antiproliferative activity against selected human melanoma and ovarian tumor cell lines, with IC(50) values of approximately 0.05-0.1 microg/mL.

Animals↗
PubMed2000

HIV-Inhibitory prenylated xanthones and flavones from Maclura tinctoria.

The organic extract of the plant Maclura tinctoria exhibited moderate anti-HIV activity. Seven prenylated phenolic derivatives were isolated from the active fractions and characterized by spectroanalytical methods. New compounds macluraxanthone B (1), macluraxanthone C (2), and dihydrocudraflavone B (8) were identified.

Anti-HIV Agents↗
PubMed2000

HIV-inhibitory cembrane derivatives from a Philippines collection of the soft coral Lobophytum species.

Bioassay-guided fractionation of an aqueous extract of a Philippine Islands collection of the soft coralLobophytum sp. concentrated its HIV-inhibitory activity into fractions rich in cembranoid diterpenes. Lobohedleolide (1), (7Z)-lobohedleolide (2), and a new compound, 17-dimethylaminolobohedleolide (3), were purified from these fractions by HPLC. The structures of compounds 1-3 were elucidated by spectroscopic analyses and by comparison of their spectral data with previously reported values. The relative stereochemistry of the gamma-lactone ring substituents of 3 was determined by 1D NOESY experiments. While several other cembranoids that contain a dimethylamino functional group have been reported from the soft coral Sinularia sp., compound 3 represents the first cembrane diterpene with this functional group isolated from a Lobophytum species. Diterpenoids 1-3 exhibited moderate HIV-inhibitory activity (EC(50) approximately 3-5 microg/mL) in a cell-based in vitro anti-HIV assay.

Animals↗
PubMed2000

New circulin macrocyclic polypeptides from Chassalia parvifolia.

Four new macrocyclic polypeptides were isolated and identified from an extract of the tropical tree Chassalia parvifolia. Circulins C-F are 29-30 amino acid cyclic peptides in which the entire primary amino acid chain is covalently cyclized via peptide bonds. Their structures were deduced from a combination of FABMS analyses, N-terminal Edman degradation, endoproteinase digestion, and amino acid analyses. All the peptides share a high degree of sequence homology and contain six cysteine residues forming three intramolecular disulfide bridges. Circulins C-F inhibited the cytopathic effects of in vitro HIV-1 infection with EC(50) values of 50-275 nM.

Alkylation↗
PubMed2000

Novel cytotoxic diterpenes from Casearia arborea.

Cytotoxicity-guided fractionation of the dichloromethane-methanol extract of the roots of Casearia arborea yielded five novel clerodane diterpenes, casearborins A-E (1-5), as well as cucurbitacin B. The presence of cucurbitacins glycosides was also detected. The absolute configuration of casearborin E was determined by X-ray crystallography.

Antineoplastic Agents, Phytogenic↗
PubMed2000

Antineoplastic agents 430. Isolation and structure of cribrostatins 3, 4, and 5 from the republic of maldives cribrochalina species.

Continued investigation of cancer-cell growth-inhibitory constituents of the blue marine sponge Cribrochalina sp. has led to discovery of cribrostatins 3 (4a), 4 (5), and 5 (4b) in 10(-5) to 10(-7) % of the wet weight. The structure of cribrostatin 3 (4a) was determined by results of high field (500 MHz) (1)H and (13)C NMR and HRMS interpretations. The same general approach to the structures of cribrostatins 4 (5) and 5 (4b) was completed by X-ray crystal structure determinations. Cribrostatins 3, 4, and 5 provided significant cancer cell line inhibitory activities. Cribrostatins 1 and 2(2) and the newly isolated cribrostatins 3-5 displayed antibacterial and/or antifungal activities.

Animals↗
PubMed2000

Outer-ring stereochemical modulation of cytotoxicity in cephalostatins.

[structure: see text] 20- and 25'-epimers of cephalostatin 7, prepared by directed unsymmetrical pyrazine synthesis, address outer-ring topographical and stability questions and intimate an oxacarbenium ion rationale for the role in bioactivity of the spiroketal (E/F, E'/F') rings of this class of antitumor agents.

Animals↗
PubMed2000

Alienation from self and others: the psychosocial problem of rural alcoholic women.

The purpose of this study was to describe women's perspectives in becoming and being alcohol dependent. Using grounded theory techniques, 14 adult Black and White women receiving treatment for alcohol addiction at rural substance abuse centers participated in an intensive interview. Data analysis focused on the identification of the basic psychosocial problem and the process of becoming alcohol dependent. The results are presented in 2 parts. Part 1, "Alienation From Self and Others," focuses on the basic psychosocial problem faced by women in becoming alcohol dependent. Part 2, "Running Away to Nowhere," on page 142 of this issue of Archives, describes the process used by women to resolve this problem.

Adult↗