PubMed Health⌕ Search

Biomedical subjects

R A Campbell

Publications and source records attributed to R A Campbell.

At least 19 recordsLinked to original sources
PubMed2006

Interference with nuclear factor kappa B and c-Jun NH2-terminal kinase signaling by TRAF6C small interfering RNA inhibits myeloma cell proliferation and enhances apoptosis.

The tumor necrosis factor receptor (TNFR)-associated factor (TRAF) family of six adaptor proteins (TRAF1-6) links the TNFR superfamily to the nuclear factor kappa B (NF-kappaB) and activator protein-1 (AP-1) transcriptional activators. Unlike other TRAFs, TRAF6 is also involved in Toll-like/interleukin (IL)-1 receptor (TIR) signal transduction. Thus, inhibition of TRAF6 function could interrupt both CD40 (TNFR family) and IL-1 growth signals, pathways critical to myeloma proliferation. To block TRAF6-mediated IL-1 signaling, we constructed small interfering RNA (siRNA) against TRAF6. We found that siRNA targeting the TRAF6 C-terminal (siTRAF6C) receptor interaction domain specifically reduced only TRAF6 protein expression, without affecting TRAF2 or 5 levels, and substantially interfered with IL-1-induced NF-kappaB and c-Jun/AP-1 activation. Inhibition by siTRAF6C was concentration-dependent. SiTRAF6C also significantly reduced myeloma proliferation and enhanced apoptosis in a similar dose-dependent fashion in vitro. More importantly, marked siTRAF6C growth inhibition was detected in vivo when these cells were implanted into the bone marrow of irradiated normal mice. In contrast, introduction of siRNA derived from the TRAF6 Zn-finger domain or an irrelevant siRNA construct failed to alter cell growth or cell death. These studies suggest that TRAF6 may be a new molecular target to block cell signal transduction important for the survival and proliferation of multiple myeloma cells.

Animals↗
PubMed2004

Tumour necrosis factor and PI3-kinase control oestrogen receptor alpha protein level and its transrepression function.

Oestrogen receptor alpha (ERalpha) is an oestrogen-activated transcription factor, which regulates proliferation and differentiation of mammary epithelial cells by activating or repressing gene expression. ERalpha is a critical prognostic indicator and a therapeutic target for breast cancer. Patients with tumours that express higher level of ERalpha have better prognosis than patients with tumours that are ERalpha negative or express lower level of ERalpha. Better prognosis in ERalpha-positive patients is believed to be due to repression of proinvasive gene expression by ERalpha. Oestrogen receptor alpha represses gene expression by transrepressing the activity of the transcription factors such as nuclear factor-kappaB or by inducing the expression of transcriptional suppressors such as MTA3. In this report, we show that ERalpha transrepresses the expression of the proinvasive gene interleukin 6 (IL-6) in ERalpha-negative MDA-MB-231 breast cancer cells stably overexpressing ERalpha. Using these cells as well as ERalpha-positive MCF-7 and ZR-75-1 cells, we show that tumour necrosis factor alpha (TNFalpha) and the phosphatidylinositol-3-kinase (PI3-kinase) modulate transrepression function of ERalpha by reducing its stability. From these results, we propose that TNFalpha expression or PI3-kinase activation lead to reduced levels of ERalpha protein in cancer cells and corresponding loss of transrepression function and acquisition of an invasive phenotype.

Blotting, Northern↗
PubMed2001

Phosphatidylinositol 3-kinase/AKT-mediated activation of estrogen receptor alpha: a new model for anti-estrogen resistance.

Estrogen receptors (ERs) mediate most of the biological effects of estrogen in mammary and uterine epithelial cells by binding to estrogen response elements in the promoter region of target genes or through protein-protein interactions. Anti-estrogens such as tamoxifen inhibit the growth of ER-positive breast cancers by reducing the expression of estrogen-regulated genes. However, anti-estrogen-resistant growth of ER-positive tumors remains a significant clinical problem. Here we show that phosphatidylinositol (PI) 3-kinase and AKT activate ERalpha in the absence of estrogen. Although PI 3-kinase increased the activity of both estrogen-independent activation function 1 (AF-1) and estrogen-dependent activation function 2 (AF-2) of ERalpha, AKT increased the activity of only AF-1. PTEN and a catalytically inactive AKT decreased PI 3-kinase-induced AF-1 activity, suggesting that PI 3-kinase utilizes AKT-dependent and AKT-independent pathways in activating ERalpha. The consensus AKT phosphorylation site Ser-167 of ERalpha is required for phosphorylation and activation by AKT. In addition, LY294002, a specific inhibitor of the PI 3-kinase/AKT pathway, reduced phosphorylation of ERalpha in vivo. Moreover, AKT overexpression led to up-regulation of estrogen-regulated pS2 gene, Bcl-2, and macrophage inhibitory cytokine 1. We demonstrate that AKT protects breast cancer cells from tamoxifen-induced apoptosis. Taken together, these results define a molecular link between activation of the PI 3-kinase/AKT survival pathways, hormone-independent activation of ERalpha, and inhibition of tamoxifen-induced apoptotic regression.

Animals↗
PubMed2001

Proemotobothrium n. g. (Cestoda: Trypanorhyncha), with the redescription of P. linstowi (Southwell, 1912) n. comb. and description of P. southwelli n. sp.

A new genus, Proemotobothrium (Trypanorhyncha: Otobothriidae), is erected to contain P. linstowi (Southwell, 1912) n. comb. (syn. Otobothrium magnum Southwell, 1924) and P. southwelli n. sp. The new genus is characterised by two bothridia, paired bothridial pits, an acraspedote scolex, elongate bulbs, four hooks per principal row, hooks 4 (4') being small and uncinate, a single, filiform, intercalary hook between each principal row and by the arrangement, in tandem, of the two or three extra hooks of the armature of the external surface of the tentacle, a pattern previously known only in the family Mixodigmatidae. The two species are distinguished from one another on the basis of measurements of the scolex and bulbs, the sizes of the hooks of the principal rows and by the number and size of the additional hooks in the linear arrays on the external surface of the tentacle.

Animals↗
PubMed2001

Grillotia australis n. sp. and G. pristiophori n. sp. (Cestoda: Trypanorhyncha) from Australian elasmobranch and teleost fishes.

Two new species of Grillotia are described from elasmobranch and teleost fishes from south-eastern Australia. G. australis n. sp., from the Australian angel shark Squatina australis. Regan, most closely resembles G. smarisgora (Wagener, 1854) and G. angeli Dollfus, 1969, differing from both species in the presence of smaller bulbs, two or occasionally three hooks in each intercalary row in the basal region, reduced to one in the metabasal region compared with four or five hooks in the metabasal region of G. smarisgora and a single hook in G. angeli, and in the limited extent of the band of hooklets on the external surface in the basal region of the tentacle, a region which is covered with hooks in G. smarisgora. Plerocerci of this species were found in the mackerel Trachurus declivis (Jenys) (site not known) from Tasmania. G. pristiophori n. sp., from the saw sharks Pristiophorus cirratus (Latham) and P. nudipinnis Günther, most closely resembles G. spinosissima Dollfus, 1969 in possessing a scolex covered with spiniform microtriches, but differs in having six rather than five hooks in each principal row, no intercalary hooks and by possessing a band of hooklets on the external surface of the tentacle which diminishes distally into a single file, rather than persisting as a band eight to nine files wide. G. pristiophori is the first trypanorhynch to be recorded from saw-sharks.

Animals↗
PubMed2001

Grillotia borealis sp. n. (Cestoda: Trypanorhyncha) from five species of Bathyraja (Rajiformes: Arhynchobatidae) in the North Pacific Ocean with comments on parasite enteric distribution.

A new trypanorhynch cestode, Grillotia borealis sp. n., is described from the spiral intestines of softnose skates of the genus Bathyraja collected from subarctic waters of the North Pacific Ocean: B. parmifera (Bean) (type host), B. aleutica (Gilbert) and B. interrupta (Gill et Townsend) from the Bering Sea and B. minispinosa Ishiyama et Ishihara and B. sminovi (Soldatov et Pavlenko) from the Sea of Okhotsk off Japan. The new species is distinguished from other species of Grillotia by possession of the following combination of characters: four hooks per principal row, hooks 4(4') distinctly separated from hooks 3(3') of principal row, principal rows separated by 13-15 intercalary hooks in 2-3 rows, hooks 2(2') and 3(3') change in form along their respective files, hooks 1(1') do not change in form along the file, a broad band of microhooks on the external tentacular face, intermediary hooks are lacking, absence of a special basal armature, origin of the retractor muscle near middle of the bulb, average scolex ratio of 1:3:2:0.1, and a hermaphroditic sac. Grillotia borealis consistently favoured the most anterior regions of the spiral intestine. Seventy-one per cent of 21 attached worms occupied the most anterior chamber of the spiral valve and 52 per cent were embedded in the anterior surface of the spiral valve whorls. Factors which may limit the distribution of G. borealis within the spiral intestine of its host are discussed. Statistically significant differences occur in the mucosal morphology of B. aleutica and B. parmifera for villus length, diameter, spatial arrangement and number per unit area along the antero-posterior axis of the spiral intestine.

Animals↗
PubMed2000

A redescription of Pintneriella Yamaguti, 1934 (Cestoda: Trypanorhyncha and an examination of its systematic position.

Specimens of Pintneriella musculicola Yamaguti, 1934 are redescribed based on paratype material and specimens subsequently allocated to the species by its describer. The cestode species is characterised by two bothridia, a typical heteroacanthous armature with a distinctive basal swelling and basal armature, a space between hook files 1 and 1', nine hooks per principal row, no intercalary hooks and bands of hooklets or chainettes but a distinctive space on the external surface of the tentacle between hook files 9 and 9'. The strobilia is unknown. The features described indicate that Pintneriella is a valid genus within the Heteracanthoidea. Its currently known morphological features do not allow its allocation to an existing family.

Animals↗
PubMed2000

Emendation of the generic diagnosis of Tylocephalum (Cestoda: Lecanicephalidea: Tetragonocephalidae), and description of Tylocephalum brooksi n. sp.

A new species of Tylocephalum is described from the spiral intestine of the cownose ray Rhinoptera bonasus taken off Venezuela. Tylocephalum brooksi n. sp. is the third species described parasitizing this host species, along with T. pingue and T. bonasum. T. brooksi is similar to congeners in the possession of a scolex with a fungiform pars apicalis, craspedote segmentation, circummedullary vitellarium, external seminal vesicle, bilobed ovary, and medioventral uterus. However, this species differs from all previously described species of Tylocephalum in having a collar around the base of the pars apicalis densely covered by large digitiform processes (microtriches?), and an internal seminal vesicle. The internal seminal vesicle is a feature currently used to differentiate Tetragonocephalum from Tylocephalum. Its presence in T. brooksi indicates that it should be considered a specific instead of a generic character. An emended diagnosis of Tylocephalum is proposed excluding this feature, along with distribution of the testes in the preovarian field and circummedullary distribution of vitelline follicles. Species of Tylocephalum and Tetragonocephalum are reviewed on the basis of original descriptions, and 2 distinct morphological groups of species defined. Species of the Tetragonocephalum group possess a combination of an acraspedote strobila, segments much longer than wide, testes limited to the region anterior to the cirrus sac, vitellarium of lateral bands, conspicuously enlarged genital atrium and pore, cirrus sac dorsal to genital atrium, and bisaccate uterus. Species of the Tylocephalum group differ from Tetragonocephalum in possession of a craspedote strobila, segments more quadrangular, testes distributed throughout the preovarian field, inconspicuous genital atrium, uniformly saccate uterus, cirrus sac lateral to genital atrium, and probable circummedullary vitellaria in all species.

Animals↗
PubMed1999

Preliminary cladistic analysis of genera of the cestode order Trypanorhyncha Diesing, 1863.

A preliminary cladistic analysis was carried out on the 49 currently recognised genera of the order Trypanorhyncha. Forty-four characters were analysed; a functional outgroup was used for scolex and strobilar characters, while Nybelinia was utilised to polarise characters related to the rhyncheal system. Eight well-resolved clades were evident in the resultant cladogram, which is compared with existing phenetic classifications. An analysis of families resulted in a similar clustering of taxa to that observed in the case of the genera. The results suggest that two key characters used in existing classifications, namely the presence of sensory fossettes on the bothridia and the development of atypical heteroacanth and poeciloacanth armatures from typical heteroacanth armatures, have occurred on several occasions. Some clades provide support for the arrangements used in current classifications. Suggestions are made for future avenues of research which might provide more robust phylogenetic data for the Trypanorhyncha.

Animals↗
PubMed1999

Systematics of the Eucestoda: advances toward a new phylogenetic paradigm, and observations on the early diversification of tapeworms and vertebrates.

Evolutionary relationships of the Eucestoda have received intense but sporadic attention over the past century. Since 1996, the landscape has dramatically changed with respect to our knowledge of the phylogenetic relationships among the tapeworms. The 2nd International Workshop for Tapeworm Systematics (IWTS) held in Lincoln, Nebraska in October of that year provided the catalyst for development of novel hypotheses for inter- and intraordinal phylogeny. The working-group structure of the 2nd IWTS and results of phylogenetic studies are briefly introduced in the present manuscript. Higher-level phylogenies derived from parsimony analysis of independent data bases representing comparative morphology or molecular sequences were largely congruent and supported monophyly for the Eucestoda. The Caryophyllidea are basal; difossate forms such as the Pseudophyllidea are primitive; tetrafossates including the Tetraphyllidea, Proteocephalidea, Nippotaeniidea, Tetrabothriidea and Cyclophyllidea are derived; and hypotheses differed in the placement of the Trypanorhyncha and the Diphyllidea. These studies may provide a foundation for resolution of inter- and intra-ordinal relationships for the tapeworms. Additionally, the first comprehensive phylogenetic hypotheses for the Pseudophyllidea, Diphyllidea, Trypanorhyncha, the paraphyletic Tetraphyllidea + Lecanicephalidea, Proteocephalidea and Cyclophyllidea were developed during and subsequent to the 2nd IWTS. The stage is now set for continued and rapid advances in our understanding of the eucestodes. These studies have also served to re-emphasise the rich genealogical diversity of tapeworms and the temporally deep history for their origin. A co-evolutionary history and radiation of eucestodes may involve deep co-speciation with vertebrate host taxa, accompanied by some level of colonisation and extinction, extending into the Palaeozoic, minimally 350-420 million years ago.

Animals↗
PubMed1999

Paroncomegas araya (Woodland, 1934) n. gen. et comb. (Cestoda: Trypanorhyncha: Eutetrarhynchidae) from the freshwater stingray Potamotrygon motoro in South America.

The trypanorhynch cestode originally designated Tentacularia araya is redescribed from its type host, Potamotrygon motoro (Potamotrygonidae), from specimens recently collected in Argentina and type material. The armature combines features of Eutetrarhynchus, Oncomegas, and Dollfusiella, indicating that its current placement in Eutetrarhynchus is incorrect and that the species represents a new genus. Paroncomegas n. gen. is proposed within the Eutetrarhynchidae Guiart, 1927, to accommodate Tentacularia araya as Paroncomegas araya n. comb. Eutetrarhynchus differs from Paroncomegas in the absence of a basal armature and basal swelling on the tentacles, from Dollfusiella by lacking macrohooks associated with the basal armature, and from Oncomegas, which possesses an asymmetrical basal swelling on the internal face of the tentaclc and a single macrohook on the external face of the basal armature. Paroncomegas is unique among these genera in possessing a chainette in the basal armature. All other genera currently recognized within the Eutetrarhynchidae can be distinguished from Paroncomegas by a distinct spatial divergence of hooks files 1(1'), resulting in a prominent space in views of the internal face. Two different morphotypes of P. araya can be distinguished in the material from Argentina, both infecting the same individual host specimens. They differ in the number and size of mature and gravid segments. Other characters concerning the tentacle armature, scolex features, and reproductive anatomy remain comparable.

Animals↗
PubMed1998

Histopathological reactions of the blue shark, Prionace glauca, to postlarvae of Hepatoxylon trichiuri (Cestoda: Trypanorhyncha: Hepatoxylidae) in relationship to scolex morphology.

Postlarvae of the cestode Hepatoxylon trichiuri (Holten, 1802) were found attached to the surface of viscera of Prionace glauca (Linnaeus, 1758) taken from Atlantic coastal waters off the south coast of Massachusetts, USA. Gross anatomy of the attachment site shows a quadripartite rim surrounding a deep pit with holes corresponding to the penetration site of each tentacle. Hyperplasia of the liver capsule into outgrowths at the attachment site conform to the attachment of the bothridia. The cuboidal epithelium of the liver capsule became columnar forming papillary outgrowths, with a dense fibrotic reaction beneath the attachment site and infiltration by leukocytes and pigment containing granulocytic cells. Blood sinusoids beneath the attachment site are greatly enlarged. Postlarvae attached to the surface of the epigonal organs of three blue sharks were not accompanied by reactions. SEM examination of the scolex of H. trichiuri postlarvae revealed fused pairs of bothridia within infolded muscular lateral rims, porose tegument devoid of microtriches and a bilateral plane of symmetry in the tentacular armature.

Animals↗
PubMed1997

Echinobothrium raschii n. sp. (Cestoda: Diphyllidea) from Rhinoraja longi (Chondrichthyes, Rajoidei) in the Bering Sea.

Echinobothrium raschii n. sp. from the spiral intestine of Rhinoraja longi in the Bering Sea, off the Aleutian Islands of Alaska is described. On the basis of the armature of the rostellum and cephalic peduncle the new species most closely resembles Echinobothrium acanthinophyllum, Echinobothrium acanthocolle, Echinobothrium coronatum and Echinobothrium helmymohamedi. Echinobothrium raschii n. sp. can be differentiated from all but E. coronatum by the possession of a continuous row of 27-36 lateral hooklets per side on the scolex and 21-26 spines per row on the cephalic peduncle. In E. acanthinophyllum there are fewer spines per row on the cephalic peduncle (13) and only 2 groups of 4 lateral hooklets per side instead of a continuous row of lateral hooklets; E. acanthocolle bears only 5 spines per row on the cephalic peduncle and has no lateral hooklets; E. helmymohamedi has 10-12 spines per row on the cephalic peduncle and bears no lateral hooklets. Echinobothrium raschii n. sp. can be distinguished from E. coronatum by number of spines per row on the cephalic peduncle (average 24 vs. 32) and testes number (17-23 vs. 9-11). The combined characters of 2 groups of 23-25 large apical hooks, a continuous alternating row of 27-36 hooklets on each side of the scolex between the groups of large apical hooks, 21-26 spines per row on the cephalic peduncle, and 17-23 testes per segment differentiates E. raschii from all other species of Echinobothrium. The prevalence of infection was 50% and mean intensity of infection was 8.7 worms per host. The current status of the genus Echinobothrium is discussed and a tabulation of the species presented.

Alaska↗
PubMed1996

Whole blood analysis of gluconeogenic amino acids for estimation of de novo gluconeogenesis using pre-column o-phthalaldehyde derivatization and high-performance liquid chromatography.

By measuring the potential glucose precursors entering and existing the liver, an estimate of the maximal rate of de novo gluconeogenesis can be made. Traditionally, measurements of gluconeogenic amino acids have been extracted from full amino acid profiles using conventional ion-exchange chromatography. These methods are labor intensive, costly procedures that do not focus on gluconeogenic amino acids. The present paper describes a method that provides an accurate whole blood gluconeogenic amino acid profile (intra-assay coefficients of variation from 0.8 to 1.1% and inter-assay coefficients of variation from 2.9 to 4.3%) using high-performance liquid chromatography with o-phthalaldehyde chemistry. This automated method is relatively fast (injection to injection time = 30 min), and linear (r2 > 0.996) for both standards and deproteinized whole blood. Furthermore, it is economical and capable of assessing gluconeogenic amino acids across a broad physiological range of concentrations using small sample volumes.

Amino Acids↗
PubMed1994

Validity and reliability testing of the Prenatal Psychosocial Profile.

Two studies of low-income pregnant women (N = 179) were done to examine the validity and reliability of the Prenatal Psychosocial Profile (PPP). The PPP, a composite of the Rosenberg Self-Esteem Scale, the Support Behaviors Inventory, and a newly developed measure of stress, is a brief, comprehensive clinical assessment of psychosocial risk during pregnancy. Construct validity of the stress scale was supported by theoretically predicted negative correlations with self-esteem, partner support, and support from others (N = 91). Convergent validity of the stress scale was demonstrated by a correlation of .71 with the Difficult Life Circumstances Scale. Adequate levels of internal consistency were found. Interrelationships between the four subscales were consistent with the underlying conceptualization, and there was beginning evidence of the factorial independence of the subscales.

Adolescent↗
PubMed1994

A PCR based method to determine the Kalow allele of the cholinesterase gene: the E1k allele frequency and its significance in the normal population.

The Kalow allele for cholinesterase is a quantitative variant of the usual gene and has been shown to result from a single base pair change in the DNA. A new method based on the polymerase chain reaction to distinguish Kalow alleles of the cholinesterase gene was developed. Using the amplification refractory mutagenesis system, two different reactions distinguished the presence of a guanine (normal E1u allele) from that of an adenine (Kalow E1k allele) at nucleotide 1615 within the coding sequences of the gene. The frequency of the Kalow allele in our sample of 51 persons was determined to be 20%. The mean total cholinesterase activity in heterozygotes was 90% of that in persons who typed as E1uE1u homozygotes. Two E1kE1k homozygotes were identified and their cholinesterase activities were the two lowest measured.

Adult↗
PubMed1994

Tentacular armature of the trypanorhynch cestode Synbothrium filicolle (Linton, 1890) (= Pterobothrium heteracanthum Diesing, 1850) and its taxonomic significance.

The armature of Synbothrium filicolle (Linton, 1890) is shown, based upon examination of Linton's specimens, by light and scanning electron microscopy. This species, a junior synonym of Pterobothrium heterocanthum Diesing 1850, represents the species upon which the genus Pterobothrium Diesing, 1850 was created, but details of the external surface of the tentacular armature have never been established with certainty. A longitudinal band of spiniform microhooks on the external tentacular surface clearly distinguishes this species from the otherwise similar Pterobothrium acanthotruncatum Escalante and Carvajal, 1984. The band merges with a triangular group of uncinate hooks in the basal armature not previously described. The 2 Brazilian species, P. crassicolle Diesing, 1850 and P. heteracanthum, used in the creation of the genus, both possess an external band of hooks. Three different modifications of the armature of the external surface have been described for species of Pterobothrium. These include a discrete band of microhooks, small groups of microhooks continuous with the intercalary rows, and the absence of a band of microhooks.

Animals↗