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Biomedical subjects

S J Cutler

Publications and source records attributed to S J Cutler.

At least 19 recordsLinked to original sources
PubMed2006

Performance of dedicated emission mammotomography for various breast shapes and sizes.

We evaluate the effect of breast shape and size and lesion location on a dedicated emission mammotomography system developed in our lab. The hemispherical positioning gantry allows ample flexibility in sampling a pendant, uncompressed breast. Realistic anthropomorphic torso (which includes the upper portion of the arm) and breast phantoms draw attention to the necessity of using unique camera trajectories (orbits) rather than simple circular camera trajectories. We have implemented several novel three-dimensional (3D) orbits with fully contoured radius-of-rotation capability for compensating for the positioning demands that emerge from different breast shapes and sizes. While a general orbit design may remain the same between two different breasts, the absolute polar tilt range and radius-of-rotation range may vary. We have demonstrated that using 3D orbits with increased polar camera tilt, lesions near the chest wall can be visualized for both large and small sized breasts (325 ml to 1,060 ml), for a range of intrinsic contrasts (three to ten times higher activity concentration in the lesion than breast background). Overall, nearly complete 3D acquisition schemes yield image data with relatively high lesion SNRs and contrasts and with minimal distortion of the uncompressed breast shape.

Breast↗
PubMed2006

Relapsing fever spirochetes Borrelia recurrentis and B. duttonii acquire complement regulators C4b-binding protein and factor H.

Relapsing fever is a rapidly progressive and severe septic disease caused by certain Borrelia spirochetes. The disease is divided into two forms, i.e., epidemic relapsing fever, caused by Borrelia recurrentis and transmitted by lice, and the endemic form, caused by several Borrelia species, such as B. duttonii, and transmitted by soft-bodied ticks. The spirochetes enter the bloodstream by the vector bite and live persistently in plasma even after the development of specific antibodies. This leads to fever relapses and high mortality and clearly indicates that the Borrelia organisms utilize effective immune evasion strategies. In this study, we show that the epidemic relapsing fever pathogen B. recurrentis and an endemic relapsing fever pathogen, B. duttonii, are serum resistant, i.e., resistant to complement in vitro. They acquire the host alternative complement pathway regulator factor H on their surfaces in a similar way to that of the less serum-resistant Lyme disease pathogen, B. burgdorferi sensu stricto. More importantly, the relapsing fever spirochetes specifically bind host C4b-binding protein, a major regulator of the antibody-mediated classical complement pathway. Both complement regulators retained their functional activities when bound to the surfaces of the spirochetes. In conclusion, this is the first report of complement evasion by Borrelia recurrentis and B. duttonii and the first report showing capture of C4b-binding protein by spirochetes.

Borrelia↗
PubMed2001

Prevention of organochlorine-induced inhibition of gap junctional communication by chaetoglobosin K in astrocytes.

Innumerable toxic substances present in the environment inhibit gap junctions, intercellular membrane channels that play fundamental roles in coordinated function of cells and tissues. Included are persistent organochlorine compounds, which pose health risks to humans and animals owing to their widespread use, bioaccumulation, and ability to inhibit gap junction channel-mediated intercellular communication in liver, lung, skin, heart, and brain cells. In this study, the organochlorine xenobiotics dieldrin and endosulfan, at micromolar concentrations, were found to inhibit gap junction-mediated intercellular communication and induce hypophosphorylation of connexin 43 in cultured rat astrocytes, the predominant cell type in the brain coupled through gap junctions. This inhibition of gap junctional communication was substantially reduced by preincubation with chaetoglobosin K (ChK), a bioactive natural produce previously shown to have ras tumor suppressor activity. Chaetoglobosin K also prevented dieldrin and endosulfan-induced hypophosphorylation of connexin 43 and prevented dieldrin-induced connexin 43 plaque dissolution in both astrocytes and cultured liver epithelial cells. The results suggest that stabilization of the native, phosphorylated form of connexin 43 by ChK may contribute to its ability to prevent organochlorine-induced inhibition of gap junction-mediated communication and dissolution of gap junction plaques within the plasma membrane.

Animals↗
PubMed2001

The effects of membership in church-related associations and labor unions on age differences in voluntary association affiliations.

PURPOSE: When compositional differences between age groups are controlled, the bivariate, curvilinear pattern of age differences in voluntary association memberships is replaced by one in which peak membership levels occur in late middle age and remain relatively stable thereafter. We sought to determine if this adjusted pattern persists when widespread memberships in two types of associations are removed: (1) church-related organizations, in which membership increases with age but may be confounded with church membership per se; and (2) labor unions, in which membership is also widespread but may not be "voluntary." DESIGN AND METHODS: Total memberships in 14 types of associations were examined using aggregated data from 12 national surveys conducted between 1974 and 1994. RESULTS: The familiar curvilinear relationship at the bivariate level appears, but in the multivariate analysis, membership levels rise from ages 18-24 through 55-59 and persist close to that level through ages 85 and older. IMPLICATIONS: The results reaffirm that age differences in voluntary association affiliations are due to age-based compositional differences; they also show, however, that the pattern observed with controls is neither driven by membership in church-related "associations" nor altered when membership in labor unions is excluded.

Adolescent↗
PubMed2000

Novel bioactive breviane spiroditerpenoids from Penicillium brevicompactum Dierckx.

The structures of four new, naturally occurring bioactive spiroditerpenoids, (+)-breviones B, C, D, and E, potential allelopathic agents, have been determined from extracts of semisolid fermented Penicillium brevicompactum Dierckx. The structures display the novel breviane spiroditerpenoid skeleton. Structure elucidation was performed by chemical transformations and by homo- and heteronuclear 2D-NMR spectral data. On the basis of combined studies of the theoretical conformations and NOEDIFF data, their relative stereochemistry is proposed. A mixed biogenesis for this novel family of spiroditerpenoids is tendered. The levels of activity shown by breviones B, C, and E in the etiolated wheat coleoptiles bioassay, especially breviones E (100% inhibition) and C (80% inhibition) both at 10(-4) M, suggest them as lead compounds for new agrochemicals.

Diterpenes↗
PubMed2000

Bioactive carotanes from Trichoderma virens.

Four new metabolites with carotane skeletons, trichocaranes A (1), B (2), C (3), and D (4), were isolated from Trichoderma virens and their structures established by the interpretation of NMR and mass spectroscopic data. The trichocaranes significantly inhibited the growth of etiolated wheat coleoptiles: 40% at 10(-4) M with 1 and 2 and 86% at 10(-3) M with 3.

Magnetic Resonance Spectroscopy↗
PubMed2000

Age differences in voluntary association memberships: fact or artifact.

OBJECTIVES: To determine if the curvilinear relationship between age and voluntary association memberships is due to compositional differences between age groups. METHODS: Data are drawn from 12 nationally representative surveys covering the period 1974-1994 and including items on membership in 16 types of associations. Age is categorized into 14 groups ranging from 18-24 through 85+. Patterns of age differences in number of association memberships are examined before and after controlling for several variables related both to age and to memberships. RESULTS: At the bivariate level, number of memberships increases through ages 40-44 and then declines fairly steadily. When controls for compositional differences are introduced, the curvilinear pattern of age differences is replaced by one showing an increasing number of memberships through ages 55-59, a slight decrease in the 60-64 age group, and then generally stable membership levels through the 85+ age group. DISCUSSION: The lower levels of voluntary association memberships of older persons consistently identified in bivariate analyses appear to be largely due to differences in compositional characteristics between the older and other age groups.

Adolescent↗
PubMed2000

Size conversion of a linear plasmid in the relapsing fever agent Borrelia duttonii.

Borreliae have genomes composed of both linear and circular replicons. We have characterized the organization of linear DNA molecules from the Borrelia duttonii strain Ly. It contains a linear one megabase chromosome and 12 linear plasmids of 11 to 200 kb in size. A variant of the strain obtained after successive in vitro cultivation in BSKII medium had a 69 kb molecule instead of the 44 kb linear plasmid. No detectable differences in the growth rates and cellular structures were found. Southern hybridization using the vsp33 gene sequence from Borrelia hermsii as a probe showed that both plasmids (69 and 44 kb molecules) contained a similar part of the sequence. The spirochetes of the parental strain cause erythrocytes to aggregate in mice blood, but the variant did not form such aggregates and seemed to have lost its infectivity in mice. Size conversion of the linear plasmid may be associated with the host-parasite relationship in mammals.

Animals↗
PubMed1999

Fractional extraction of compounds from grape seeds by supercritical fluid extraction and analysis for antimicrobial and agrochemical activities.

White grape seeds were subjected to sequential supercritical fluid extraction. By increasing the polarity of the supercritical fluid using methanol as a modifier of CO(2), it was possible to fractionate the extracted compounds. Two fractions were obtained; the first, which was obtained with pure CO(2), contained mainly fatty acids, aliphatic aldehydes, and sterols. The second fraction, obtained with methanol-modified CO(2), had phenolic compounds, mainly catechin, epicatechin, and gallic acid. The fractions were bioassayed. Antimicrobial activities were checked on human pathogens, and a high degree of activity was obtained with the lipophilic fraction. Agrochemical activities on phytopathogenic fungi and activities on the etiolated wheat coleoptile bioassay were also checked. The more polar fraction was active in the latter bioassay.

Bacteria↗
PubMed1999

Successful in vitro cultivation of Borrelia duttonii and its comparison with Borrelia recurrentis.

Borrelia duttonii, the cause of East African tick-borne relapsing fever, has until now been refractory to growth in laboratory media. This spirochaete has only be propagated in mice or by tissue culture, restricting both yield and purity of cells available for research. The successful isolation of five clinical isolates of B. duttonii from patients in Central Tanzania and their comparison with Borrelia recurrentis is reported. Electron microscopy revealed spirochaetal cells with pointed ends, a mean wavelength of 1.8 microns with an amplitude of 0.8 micron, similar to the findings for B. recurrentis. Cells contained 10 periplasmic flagella inserted at each end of the spirochaete, again comparable with the counts of 8-10 flagella found in B. recurrentis. PFGE revealed a chromosome of approximately 1 Mb, a large plasmid of approximately 200 kb, and a small plasmid of 11 kb in all strains of B. duttonii and in B. recurrentis. B. duttonii possessed a further 7-9 plasmids with sizes ranging from 20 to 90 kb. In two isolates of B. duttonii, the profiles were identical. In contrast, all 18 isolates of B. recurrentis fell into one of five plasmid patterns with 3-4 plasmids ranging from 25 to 61.5 kb in addition to those of 11 and 200 kb described above. Analysis of the SDS-PAGE profiles of B. duttonii strains revealed a high-molecular-mass band of 33.4-34.2 kDa in four strains (variable large protein, VLP) and a low-molecular-mass band of 22.3 kDa in the remaining strain (variable small protein, VSP). This resembles the protein profiles found in B. recurrentis. The G + C ratio of B. duttonii was 27.6 mol%. Nucleotide sequence of the rrs gene (16S rRNA) from four B. duttonii isolates revealed 100% identity among these strains and 99.7% homology with three strains deposited by others in GenBank. The rrs gene of eight representative clinical isolates of B. recurrentis confirmed their close similarity with B. duttonii.

Bacteriological Techniques↗
PubMed1998

Pharmacological evaluation of 1-(carboxymethyl)-3,5-diphenyl-2-methylbenzene, a novel arylacetic acid with potential anti-inflammatory properties.

OBJECTIVE AND DESIGN: 1-(Carboxymethyl)-3,5-diphenyl-2-methylbenzene (CDB), a novel arylacetic acid, was evaluated in vivo for its ability to inhibit acute and chronic inflammation as well as acute pain. MATERIALS AND METHODS: The effects of CDB were evaluated using the following assays: 1) acute inflammation induced by the injection of carrageenan, bradykinin and serotonin into the subplantar region of the hind paw of rats; 2) chronic inflammation produced by the injection of Mycobacterium butyricum into the base of the tail of rats; 3) acute pain induced by the i.p. injection of phenyl-p-quinone into mice resulting in the production of writhes; 4) cyclooxygenase (COX) activity, including COX-1 and COX-2, evaluated using whole blood; and 5) activity of peptidylglycine alpha-monooxygenase (PAM) isolated from Xenopus laevis skin. RESULTS: CDB (10 to 100mg/kg s.c.) produced a dose-dependent inhibition of carrageenan edema (ED50 of 41 mg/ kg at 3 h) which continued for up to 12 h. Using a therapeutic dosing regimen, this compound inhibited hind paw inflammation (>70%) and arthogram scores in rats with adjuvant-induced arthritis. This compound also possessed significant analgesic activity in mice (70% inhibition with 50mg/kg). CDB, however, lacked inhibitory activity on bradykinin and serotonin-induced edema. In addition, CDB significantly inhibited COX-I activity (IC50 approximately = 17 microM) while having only a weak inhibitory activity on both COX-2 and PAM activity. CONCLUSIONS: CDB is an effective anti-inflammatory/analgesic agent whose mechanism of action appears to be associated with inhibition of COX-1 activity.

Acetates↗
PubMed1998

Variable major lipoprotein is a principal TNF-inducing factor of louse-borne relapsing fever.

Massive release of tumor necrosis factor is responsible for the potentially fatal larisch-Herxheimer reaction that follows antibiotic treatment of relapsing fever due to Borrelia recurrentis. We have undertaken the quantitative purification of the components of B. recurrentis that stimulate human monocytes to produce tumor necrosis factor. We show that the predominant factor inducing tumor necrosis factor is a variable lipoprotein homologous to the variable major protein of B. hermsii. We found antibodies to different forms of variable major protein in two patients with louse-borne relapsing fever. The three purified variable major proteins studied here differ in their ability to induce tumor necrosis factor production, which may partly explain the variable clinical severity of borrelial infection. These results may be of considerable relevance for the pathogenesis of Lyme disease and other forms of human borreliosis.

Amino Acid Sequence↗
PubMed1997

Borrelia recurrentis characterization and comparison with relapsing-fever, Lyme-associated, and other Borrelia spp.

Borrelia recurrentis, the cause of louse-borne relapsing fever, has until recently been considered noncultivable, which has prevented characterization of this spirochete. We successfully cultivated 18 strains from patients with louse-borne relapsing fever and present the initial characterization of these isolates. Electron microscopy revealed spirochetal cells with pointed ends, an average wavelength of 1.8 microns, an amplitude of 0.8 micron, and 8 to 10 periplasmic flagella. The G+C ratio was 28.4 mol%. Whole DNA-DNA hybridizations showed similarity between the isolates of B. recurrentis but not with Borrelia hermsii, Borrelia parkeri, Borrelia turicatae, or the Lyme-associated borreliae. Sequencing studies of both the flagellin and 16S RNA genes revealed that the greatest similarity was between B. recurrentis and Borrelia duttonii. Analysis of the sodium dodecyl sulfate-polycarylamide gel electrophoresis profiles of strains revealed four groups based on the position of a major protein band (one of the groups showed some heterogeneity and was subdivided into four subgroups). Pulsed-field gel electrophoresis revealed five distinct patterns.

Borrelia↗
PubMed1996

Anticipatory dementia: a link between memory appraisals and concerns about developing Alzheimer's disease.

This exploratory study examines the link between memory appraisals and personal concerns about developing Alzheimer's disease. The sample of persons ages 40-60 includes adult children with a living parent who has Alzheimer's disease (N = 25) and a matched group with no family history of dementia (N = 25). Using two composite measures of memory appraisals, the results show significant bivariate and multivariate relationships between self-assessments of memory functioning and concerns about developing the disease. The findings also suggest that negative memory appraisals evoke concerns about developing Alzheimer's disease within both of the subsamples.

Adult↗
PubMed1996

Phylogenesis of relapsing fever Borrelia spp.

The phylogenetic relationships of 20 relapsing fever (RF) Borrelia spp. were estimated on the basis of the sequences of rrs genes. Complete sequences were aligned and compared with previously published sequences, and the similarity values were found to be 97.7 to 99.9%. Phylogenetic trees were constructed by using the three neighbor-joining, maximum-parsimony, and maximum-likelihood methods. The results of the comparative phylogenetic analysis divided the RF Borrelia spp. into three major clusters. One cluster included Borrelia crocidurae, Borrelia duttonii, Borrelia recurrentis, and Borrelia hispanica. Another cluster comprised tow main branches with Borrelia coriaceae, Borrelia lonestari, and Borrelia miyamotoi on one side and Borrelia parkeri, Borrelia turicatae, and Borrelia hermsii on the other side. Borrelia anserina constituted the third cluster. The phylogenetic position of Borrelia persica was more uncertain. These results suggested that the taxonomy of these spirochetes should be revised. To overcome the problems of culturing the spirochetes, RF Borrelia primers were defined. Following PCR amplification of the rrs gene, restriction length fragment polymorphism could be used to distinguish between RF Borrelia strains.

Animals↗
PubMed1996

Racial differences in the household composition of elders by age, gender, and area of residence.

Using census data and an innovative technique for describing the composition of households from the perspective of elders, this research provides a more detailed description of race differences in living arrangements of older persons than has previously existed. In addition, cross tabulations of race with other factors known to influence household composition (gender, age, and area of residence) are examined. While white women are more likely than black women to live alone, the reverse is true among men. Whites are more likely than blacks to live in married-couple-only households, and blacks are more likely than whites to live in multigenerational households, although these differences decrease with advancing age. Blacks are also more likely than whites to live with collateral kin or non-kin only, although these categories comprise small proportions of the population. Implications of these differences for caregiving and quality of life among older persons are discussed.

Black or African American↗