Biomedical subjects

M A Nowell

Publications and source records attributed to M A Nowell.

11 recordsLinked to original sources

PubMed2006

Interleukin-6 signalling in juvenile idiopathic arthritis is limited by proteolytically cleaved soluble interleukin-6 receptor.

OBJECTIVES: Interleukin-6 (IL-6) exerts multiple effects on chondrocytes and fibroblasts within the joint and is associated with disease activity in juvenile idiopathic arthritis (JIA). Although these cells express the ubiquitous signalling receptor for all IL-6-related cytokines, gp130, they do not express a cognate IL-6 receptor. Consequently, IL-6 responses within these cells occur via IL-6 trans-signalling relying on the presence of a soluble receptor (sIL-6R). Levels of sIL-6R in vivo are governed by either proteolytic cleavage (PC) of cognate receptor or by differential sIL-6R mRNA splicing (DS). The aim of this study was to evaluate the contribution of both isoforms to clinical parameters associated with IL-6 signalling in JIA. METHODS: IL-6, sIL-6R and DS-sIL-6R were measured by ELISA in serum and synovial fluid (SF) samples from 86 JIA patients. These data were related to indicators of inflammation-erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) and compared between patients stratified by subtype, age and disease duration. RESULTS: SF IL-6 significantly correlated with general indicators of activity (ESR and CRP) and SF PC-sIL-6R to a lesser degree with CRP. When the IL-6:sIL-6R ratio was calculated as an indicator of the potential for IL-6 signalling within the joint, 33% of SF samples showed a ratio >1 indicating saturation of sIL-6R by IL-6. Mean DS-sIL-6R levels were 0.71 ng/ml, whereas PC-sIL-6R levels constituted the majority of sIL-6R at 20.89 ng/ml. CONCLUSIONS: IL-6 trans-signalling within the joints of JIA patients is predominantly governed by the presence of PC-sIL-6R, and the data provided suggest that synovial levels of IL-6 and sIL-6R would be sufficient to drive IL-6 responses in chondrocytes and synovial fibroblasts.

Adolescent↗

PubMed2001

Characterization of a sea bream (Sparus aurata) thyroid hormone receptor-beta clone expressed during embryonic and larval development.

A clone encoding thyroid hormone receptor-beta (TR-beta) was isolated from a sea bream (Sparus aurata) ovary cDNA library. Sea bream (sb)TR-beta is closely related to its counterparts from other vertebrates and, like them, preferentially binds T3 rather than T4. However, the putative sbTR-beta protein contains a nine-amino-acid insert that is also present in the corresponding proteins from flounder and salmon but absent in TR-betas from zebrafish and terrestrial vertebrates. Semiquantitative RT-PCR analysis showed that sbTR-beta transcripts begin to accumulate during gastrulation and increase markedly in quantity up to the period around hatch (ca. 40 h postfertilization) before declining slightly. In adult tissues, TR-beta mRNA was present in approximately equal quantities in heart, intestine, brain, kidney, skeletal muscle, liver, and gill. The significance of the relatively strong expression of TR-beta during sea bream embryogenesis is discussed.

Amino Acid Sequence↗

PubMed2001

Thyroid hormones in growth and development of fish.

The thyroid hormones (THs), thyroxine (T(4)) and triiodothyronine (T(3)) are products of the thyroid gland in all vertebrates. Their role in early development and metamorphosis is well established in mammals and amphibians, respectively, and recently several studies in fish have highlighted the importance of THs during flatfish metamorphosis. THs are present in high quantities in fish eggs and are presumably of maternal origin. During embryogenesis the concentration of T(4) and T(3) in the eggs decrease until endogenous production starts. Thyroid hormone receptors (TR) have been isolated from several teleosts and in common with tetrapods two receptor isoforms have been identified, TR alpha and TR beta. Both the receptors are expressed in early embryos and larvae of the Japanese flounder (Paralichthys olivaceus), zebrafish (Danio rerio) and seabream (Sparus aurata) although a different temporal pattern is apparent. The role of THs and TRs in fish embryogenesis, larval development and during metamorphosis will be discussed.

Amino Acid Sequence↗

PubMed1999

Caenorhabditis elegans as a biomonitor for immunological stress in nematodes.

An experimental system has been developed using Caenorhabditis elegans (Secernentea: Rhabditida), to monitor immunological stress in nematodes. The transgenic C. elegans strain PC72 carries a lacZ reporter gene fused to a C. elegans hsp16-1 gene, which is inducible for beta-galactosidase activity at the heat stress temperature of 26 degrees C. The investigate the possibility of using PC72 to monitor immunological stress, its surface coat was targeted, to mimic immune attack, by raising immune sera against surface coat components selectively removed by the cationic detergent cetyltrimethylammoniunm bromide. Initially, a highly significant induction of beta-galactosidase activity was seen in PC72 incubated in either surface-reactive or naïve rabbit serum. Complement (C3) was detected over the entire surface of adult PC72 and was thought to be responsible for stress-induction with naïve sera. When the immunoglobulin (Ig)G fraction of naïve sera was used in isolation, no stress-induction was seen. In contrast, a two-fold increase in beta-galactosidase activity was seen in the presence of surface-reactive IgG (SR-IgG) which recognised surface components of between 6 and 40 kDa in western blot. The belief that surface reactive IgG could induce a stress response was reinforced by analysis of hsp-16 protein expression. Cationised ferritin was then used to assess whether stress-induction was truly a surface reactive event; binding of cationised ferritin to the nematode surface also resulted in two-fold induction of beta-galactosidase activity. To investigate the downstream biological effects of stress induction, worm growth and fecundity were measured in the presence of IgG preparations. A significant reduction was seen in both worm length and fecundity only when larvae were incubated in surface-reactive IgG, compared to both naïve IgG and K-medium controls. In conclusion, it would appear that C. elegans is a suitable model to monitor the induction of immunological stress at the level of the nematode surface coat. Given the ability of nematode surface antigens to protect the vaccinated host in animal model systems, and the close phylogenetic relationships which exist between C. elegans and nematodes of medical and veterinary importance, it is conceivable that the immunological targets in or on the surface of C. elegans warrant rapid identification.

Animals↗

PubMed1990

Varied MR appearance of autism: fifty-three pediatric patients having the full autistic syndrome.

Fifty-three autism patients ranging in age from 2 to 22 yr with a mean age of 9 yr were evaluated by MR imaging over a 3-yr study period. Sagittal, axial, and coronal spin-echo and short TI inversion recovery scans were performed on a 0.5 Tesla (Picker Inc., Cleveland, OH) system. Results were compared to 32 control patients age range 1 to 17 yr, mean 8.5 yr. MR scans were evaluated by three neuroradiologists. Measurements of midsagittal vermian height and AP diameter were performed. Subjective estimates were made of ventricular size, amygdala size, fourth ventricular size, and vermian shape. Results were correlated with clinical presentation, course, and lab analyses by a pediatric neurologist. MR findings did not present a single pattern capable of predicting the presence or severity of autism. The constellation of MR findings in this group of 53 patients was highly variable, thus we advise caution in the interpretation of MR images in autistic patients. Autism is a heterogeneous disease entity containing different clinical subgroups, which do not manifest similar radiologic pictures.

Adolescent↗

PubMed1988

Focal cortical dysplasia on magnetic resonance imaging: a case report.

A case report of an 11 years old boy with new onset of a seizure disorder is presented. A computed tomography scan demonstrated a noncalcified, nonenhancing focal region of abnormal cortex. A magnetic resonance imaging scan delineated both an isointense area of abnormally thickened gyri and linear areas of abnormal high signal intensity in the subjacent white matter. A review of the radiologic and pathologic literature suggests that this lesion represents the entity focal cortical dysplasia as described by Taylor, et al. This abnormality is part of a spectrum of disorders including hamartomas (of tuberous sclerosis), focal cortical dysplasia and heterotopias.

Astrocytes↗

PubMed1988

MR imaging of white matter disease in children.

Twenty-three pediatric patients with white matter abnormalities on MR images were evaluated retrospectively to assess the contribution of MR compared with CT in diagnosing these conditions. In addition, the MR findings in major categories of white matter diseases were analyzed for sensitivity in detecting the presence of an abnormality. White matter disease categories included demyelinating disease (five cases), dysmyelinating disease (eight cases), developmental white matter abnormalities (four cases), and white matter abnormalities of unknown origin (idiopathic) (six cases), as seen on long TR images. We found that MR is not more sensitive than CT in detecting disease in the demyelinating or dysmyelinating categories, although it is more sensitive than CT in detecting the degree of disease present. In cases of developmental delay, MR is distinctly more useful than CT in demonstrating abnormalities of myelination. And in the idiopathic group, MR detected the presence of focal white matter abnormalities on long TR images in children with neurologic complaints and normal CT. MR may serve to redefine and broaden the spectrum of reported imaging abnormalities in pediatric patients.

Adolescent↗

PubMed1987

Giant cystic craniopharyngiomas.

Three cases of giant cystic craniopharyngiomas with large areas of extension beyond the suprasellar area are presented. The magnetic resonance (MR) appearance in one case is described. These giant tumors had large, multilobulated cysts that comprised the bulk of the tumors. In one case, there was an unusual extension of the large tumor cyst into the lateral ventricle. In two cases, the tumors extended to the level of the foramen magnum. On CT, the cyst contents of these two tumors were hyperdense and became hypodense postoperatively. All three tumors harbored calcifications in the form of clumps in the suprasellar region and rim calcifications around the cysts. None of the tumors exhibited contrast enhancement. A literature review of the radiographic features of craniopharyngiomas is discussed.

Calcinosis↗

PubMed1987

Immature brain: spin-echo pulse sequence parameters for high-contrast MR imaging.

Appropriate spin-echo (SE) pulse sequence parameters generate magnetic resonance (MR) images with very high gray matter/white matter contrast in neonates and young infants. In these young patients, long SE sequences with a repetition time of 3,000-3,500 msec and multiple echoes with the longest echo time of 120-160 msec are employed to yield high-contrast images. A high-contrast MR image of a 1-month-old infant is presented.

Brain↗

PubMedDate not supplied

Predisposition to hookworm infection in Papua New Guinea.

Reinfection with hookworm (Necator americanus) following chemotherapy was studied over 8 years in a rural village in Madang Province, Papua New Guinea. Faecal egg counts were performed on up to 202 individuals in July 1988, August 1990 and November 1996; the study population was treated after sampling in 1988 and 1990. Reinfection burdens in 1996 did not differ significantly from pretreatment burdens (in 1988), and were significantly higher than burdens in 1990. However, the prevalence of hookworm infection was significantly lower in 1996 than in either 1988 or 1990. There was significant predisposition to high or low hookworm burden between 1990 and 1996; this predisposition was stronger in children than adults. However, there was no detectable predisposition between 1988 and 1996 in individuals who had been treated 2 or more times between surveys. The mean weight of adult hookworms in individual hosts was measured in 1988 and 1990 using worms expelled after chemotherapy. There was a significant positive correlation between mean male hookworm weight in the 2 years, suggesting that individual hosts are predisposed to infection with heavy or light hookworms. These data suggest that differences in host susceptibility are involved in generating predisposition, but that longer-term variation in either exposure or susceptibility limits the period over which significant predisposition can be detected.

Adolescent↗

PubMedDate not supplied

Initial experience with fast low-angle multiecho (FLAME) imaging of the central nervous system.

Fast low-angle multiecho (FLAME) imaging uses partial flip angles of less than 90 degrees with 180 degrees radiofrequency refocusing pulses. The partial flip angle permits imaging with shorter repetition time (TR) values on the order of 750-1,000 ms for 30 degrees angles with image contrast characteristics identical to those obtained with conventional 90-180 degrees schemes and TRs on the order of 2,500 ms. The approximately threefold reduction in imaging time is accompanied by a decrease in signal-to-noise ratio. In many circumstances, however, this trade-off may produce entirely acceptable images of the CNS at a significant reduction in imaging time.

Central Nervous System Diseases↗