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Biomedical subjects

A Chawla

Publications and source records attributed to A Chawla.

At least 19 recordsLinked to original sources

Paediatric PNET: pre-surgical MRI features.

AIM: To describe the preoperative magnetic resonance imaging (MRI) characteristics of primitive neuroectodermal tumours (PNETs), in particular the diffusion-weighted imaging (DWI), MR spectroscopy (MRS) features and cerebrospinal fluid (CSF) tumour dissemination. MATERIAL AND METHODS: Twelve patients with PNETs were reviewed: nine with medulloblastoma and three with supratentorial PNETs (SPNETs). The MRI examination included contrast-enhanced intracranial and spinal MRI, and in some patients, gradient recalled echo, fluid-attenuated inversion recovery (FLAIR), DWI, and MRS. RESULTS: All PNETs were either hypointense or isointense on T1-weighted images. Ten of the 12 tumours were either isointense or hypointense on T2-weighted images, and 11 were isointense on FLAIR images. Patients with SPNETs had large, vascular and haemorrhagic tumours. On DWI, all PNETs were hyperintense and had restricted apparent diffusion coefficient. MRS (two patients with medulloblastoma and one with a SPNET), showed elevated choline, decreased N-acetyl aspartate, and a small taurine peak in all three patients. Intraspinal tumour dissemination, visible as uniform or nodular enhancement coating the conus medullaris, was detected in six of 12 patients, two of whom also had intracranial dissemination. CONCLUSION: PNETs have a characteristic imaging appearance on FLAIR, DWI and MRS, which may help in differentiating these highly cellular neoplasms from other tumours. There is CSF tumour dissemination in a high proportion of patients, and spinal imaging is important for disease staging and to formulate treatment protocols.

Aspartic Acid↗

Human immunodeficiency virus (HIV) antibody avidity testing to identify recent infection in newly diagnosed HIV type 1 (HIV-1)-seropositive persons infected with diverse HIV-1 subtypes.

A guanidine-based antibody avidity assay for the identification of recently acquired human immunodeficiency virus type 1 (HIV-1) infection was evaluated. The kinetics of maturation of antibody avidity were determined prospectively in 23 persons undergoing acute seroconversion followed for up to 1,075 days. Avidity indices (AI) of <or=0.75 and <or=0.80 reproducibly identified seroconversion within the previous 125 (95% confidence interval [CI], 85 to 164) and 142 (95% CI, 101 to 183) days, respectively. To validate the assay, 432 serum samples from newly diagnosed patients were tested by both the avidity assay and the detuned assay. Results were highly concordant (kappa value for agreement, 0.85). The avidity assay was subsequently used to screen 134 consecutive newly diagnosed patients, including 55/134 (41%) infected with non-B subtypes (A, C, D, G, CRF01, CRF02, CRF06, CRF13, and CRF16). In this cohort, 25/79 (32%) persons with the B subtype and 7/55 (13%) with non-B subtypes showed an AI of <or=0.75, and there were 16/25 (64%) and 3/7 (43%) persons, respectively, with a documented history of acute seroconversion illness within the predicted seroconversion interval. An AI of <or=0.75 was also observed for four patients (three with the B subtype and one with a non-B subtype) who presented with AIDS-defining conditions. In multivariate analysis, an AI of <or=0.75 was associated with younger age, higher HIV-1 plasma RNA load, and being born in the United Kingdom or Ireland rather than in Africa but not with gender, ethnicity, risk group, HIV-1 subtype, or CD4 counts. In conclusion, HIV antibody avidity testing provides a reliable method for identifying recently acquired HIV-1 infection. Results are affected by advanced disease and should therefore be interpreted in the context of other clinical parameters.

Adult↗

Intraosseous haemangioma of the proximal femur: imaging findings.

Haemangiomas of bone are uncommon lesions, accounting for approximately 1% of all primary bone tumours. The most frequent sites of involvement are the calvaria and the vertebral column. When haemangiomas involve long tubular bones, they are usually found in the diaphysis or metadiaphysis. Juxta-articular or epiphyseal location for a long bone haemangioma is rare. We present the imaging findings in a case of a histopathologically proven juxta-articular intraosseous haemangioma of the proximal femur. We believe ours is the first report of a haemangioma involving the proximal end of the femur.

Adult↗

Symptomatic accessory soleus muscle: diagnosis and follow-up on magnetic resonance imaging.

The accessory soleus muscle is a rare anatomical variant which, although congenital in origin, may manifest in the second and third decades of life as a painful ankle mass or an asymptomatic ankle soft tissue swelling. We report a symptomatic accessory soleus muscle in a 21-year-old male soldier that was diagnosed and followed-up on MRI. Initial MRI showed a mass with signal characteristics of normal muscle, but in an abnormal location. There was increased intrafascial fluid and perimuscular oedema around the accessory soleus muscle. Following conservative treatment, repeat MRI showed resolution of this intrafascial fluid collection and perimuscular oedema, concurrent with relief of the patient's painful symptoms.

Ankle Injuries↗

Minimally important differences were estimated for the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) instrument using a combination of distribution- and anchor-based approaches.

OBJECTIVE: To estimate minimally important differences (MIDs) on the Functional Assessment of Cancer Therapy-Colorectal (FACT-C) instrument using anchor- and distribution-based methods. STUDY DESIGN AND SETTING: Preliminary MIDs were generated for FACT-C scores based on published results for two samples (n = 60 and n = 63) from the FACT-C validation study. Preliminary MIDs were confirmed using data from a Phase II randomized controlled clinical trial (n = 104) and a population-based observational study (n = 568). MIDs were estimated for the colorectal cancer subscale (CCS); the FACT-C Trial Outcome Index (TOI-C), which is the sum of the CCS, physical well-being, and functional well-being subscales; and the FACT-C total score. Both cross-sectional and longitudinal analyses were used. RESULTS: MIDs were stable across the different patient samples. The recommended MIDs ranged from 2 to 3 points for the CCS, 4 to 6 points for the TOI-C, and 5 to 8 points for the FACT-C total score. CONCLUSIONS: MIDs can enhance the interpretability of FACT-C scores, and they can be used to provide a basis for sample size estimation and to determine clinical benefit in combination with other measures of efficacy. General guidelines for estimating MIDs for other FACT instruments are suggested.

Adult↗

Female genital tuberculosis: hysterosalpingographic appearances.

Genital tuberculosis is an important cause of infertility in developing countries and hysterosalpingography (HSG) is the initial procedure performed for the evaluation. Reviewing 37 cases of female genital tuberculosis, we encountered various appearances on HSG. Of 579 HSGs performed over a period of 4 years, 492 (85%) were performed as part of infertility work up. Genital tuberculosis was found in 6.3% of all the patients who underwent HSGs and 7.5% of all patients investigated for infertility. The various features of proven tuberculosis cases are illustrated in this pictorial review. We briefly discuss the pathology and these appearances along with radiopathological correlation.

Adult↗

MRI of spinal intradural arachnoid cyst formation following tuberculous meningitis.

Secondary intradural arachnoid cyst involving the spine is uncommon. It is usually secondary to trauma, haemorrhage, surgery or inflammation. We present two cases of treated tuberculous meningitis, which presented with gradual onset of quadriplegia and paraplegia, respectively. MRI revealed intradural (cervical and thoracic) arachnoid cysts (ventral and dorsal to the spinal cord) with myelomalacic cord changes. Ventral location of such spinal arachnoid cysts, and being secondary to tuberculous arachnoiditis are distinctively uncommon features. The rarity of this condition and the relevance of MRI in the accurate diagnosis have been discussed here.

Adult↗

Clinics in diagnostic imaging (100). Migrated pharyngeal fish bone.

A 71-year-old man presented with a suspected swallowed fish bone. The lateral radiograph of the neck showed a curvilinear radio-opaque density in the swollen pre-vertebral soft tissues. The diagnosis of a migrated fish bone was confirmed on computed tomography and during subsequent surgery. The patient made a good recovery. As calcified normal structures, particularly the laryngeal cartilages, can mimic abnormal radio-opaque foreign bodies, it is important to be able to recognise the normal calcified structures seen on the neck radiograph. A sound knowledge of radiological anatomy is required in order to avoid unnecessary investigation and to provide prompt and appropriate management.

Aged↗

Isolated solitary vertebral body tuberculosis--study of seven cases.

AIM: To describe the magnetic resonance imaging (MRI) findings in isolated solitary vertebral body tuberculosis. Also to emphasize tuberculosis as an important entity, besides neoplasms, in the differential diagnosis of pathologies involving a single vertebral body. MATERIAL AND METHODS: The clinical and imaging features of seven patients (four men and three women; age range 18-60 years), with proved solitary vertebral body tuberculosis were retrospectively studied. RESULTS: Isolated solitary vertebral body tuberculosis is seen in only 1.69% of the total proven cases of spine tuberculosis seen in our institute between 1993 and 2002. All patients presented with constitutional symptoms and localized pain and tenderness. MRI showed decreased signal intensity on T1-weighted images and increased signal intensity on T2-weighted images. Cortical break was seen in three patients of whom epidural and pre-vertebral extensions were seen in one each. CONCLUSIONS: Although tuberculosis affecting a solitary vertebral body is rare it should be considered as an important differential diagnosis, besides neoplasms. In these cases MRI serves as the best imaging technique available for diagnosis. However, confirmation can only be made on histopathology or culture of the specimen.

Adolescent↗

Increased engraftment and GVHD after in utero transplantation of MHC-mismatched bone marrow cells and CD80low, CD86(-) dendritic cells in a fetal mouse model.

BACKGROUND: Bone marrow transplantation (BMT) is the only known cure for a variety of inherited diseases and requires the administration of high doses of immunosuppressive and myeloablative therapy. Because the fetus is immunoincompetent early in gestation, in utero stem cell transplantation (IUT) could avoid the need for this toxic conditioning. A major limitation to date of IUT is the low level of engraftment and failure to induce tolerance. Dendritic cells (DC) are considered very potent antigen-presenting cells, but DC progenitors (pDC) are strongly tolerogenic. METHODS: We examined the effect of donor pDC on the degree of engraftment and tolerance induction after IUT. Bone marrow-derived pDC (CD80low, CD86-) from male C57BL/6 mice (H2b) were injected with and without donor bone marrow (BM) intraperitoneally into 13 to 15-day BALB/c (H2d) fetuses. Engraftment was determined by flow cytometry and quantitative polymerase chain reaction and tolerance by skin grafts and the mixed lymphocyte reaction. RESULTS: At 1-month posttransplant, mice that received BM+pDC showed a higher degree of engraftment (29+/-46%) than mice that received pDC-enriched cells or BM cells alone (0.11+/-0.70% and 1.71+/-1.66%, respectively, P<0.001). However, 5/19 recipients of BM+pDC died within 6 weeks; 4/5 had significant donor cell engraftment in blood and/or tissues. Also, these mice had evidence of graft-versus-host disease (GVHD). Two mice out of 15 long-term survivors in the BM+pDC group had virtually complete replacement of host with donor hematopoietic cells. Skin grafts and mixed lymphocyte reaction studies showed no durable tolerance induction other than in the two fully engrafted recipients of BM+pDC. CONCLUSIONS: These results suggest that donor pDC, along with donor BM, can have a significant impact on engraftment of MHC-mismatched donor cells associated with an increased incidence of GVHD. However, marrow-derived pDC do not result in an increase in tolerance induction in utero even when microchimerism is present.

Animals↗

Nuclear receptors and lipid physiology: opening the X-files.

Cholesterol, fatty acids, fat-soluble vitamins, and other lipids present in our diets are not only nutritionally important but serve as precursors for ligands that bind to receptors in the nucleus. To become biologically active, these lipids must first be absorbed by the intestine and transformed by metabolic enzymes before they are delivered to their sites of action in the body. Ultimately, the lipids must be eliminated to maintain a normal physiological state. The need to coordinate this entire lipid-based metabolic signaling cascade raises important questions regarding the mechanisms that govern these pathways. Specifically, what is the nature of communication between these bioactive lipids and their receptors, binding proteins, transporters, and metabolizing enzymes that links them physiologically and speaks to a higher level of metabolic control? Some general principles that govern the actions of this class of bioactive lipids and their nuclear receptors are considered here, and the scheme that emerges reveals a complex molecular script at work.

Animals↗

Hepatitis C virus replication is directly inhibited by IFN-alpha in a full-length binary expression system.

Hepatitis C virus (HCV) is a leading cause of chronic hepatitis, cirrhosis, and hepatocellular carcinoma. The absence of culture systems permissive for HCV replication has presented a major bottleneck to antiviral development. We sought to recapitulate the early steps in the life cycle of HCV by means of DNA-based expression of viral genomic sequences. Here we report expression of replicating HCV RNA by using a, to our knowledge, novel binary expression system in which cells were transfected with a T7 polymerase-driven full-length HCV cDNA plasmid containing a cis-acting hepatitis Delta ribozyme to control 3' cleavage, and infected with vaccinia-T7 polymerase. HCV genomic and replicative strand synthesis, in addition to protein synthesis, was detectable and depended on full-length HCV sequences. Moreover, the system was capable of generating HCV RNA quasispecies, consistent with the action of the low-fidelity HCV NS5B RNA polymerase. IFN-alpha, but not ribavirin, directly inhibited the viral replicative cycle in these cells, identifying the virus itself and not solely the immune system as a direct target of IFN action. The availability of a cell-based test for viral replication will facilitate screening of inhibitory compounds, analysis of IFN-resistance mechanisms, and analysis of virus-host cell interactions.

Amantadine↗

Signaling complexes of the FERM domain-containing protein GRSP1 bound to ARF exchange factor GRP1.

GRP1 is a member of a family of proteins that contain a coiled-coil region, a Sec7 homology domain with guanosine nucleotide exchange activity for the ARF GTP-binding proteins, and a pleckstrin homology domain at the C terminus. The pleckstrin homology domain of GRP1 binds phosphatidylinositol (3,4,5) trisphosphate and mediates the translocation of GRP1 to the plasma membrane upon agonist stimulation of PI 3-kinase activity. Using a (32)P-labeled GRP1 probe to screen a mouse brain cDNA expression library, we isolated a cDNA clone encoding a GRP1-binding partner (GRSP1) that exists as two different splice variants in brain and lung. The GRSP1 protein contains a FERM protein interaction domain as well as two coiled coil domains and may therefore function as a scaffolding protein. Mapping experiments revealed that the interaction of GRP1 and GRSP1 occurs through the coiled coil domains in the two proteins. Immunodepletion experiments indicate that virtually all of the endogenous GRSP1 protein exists as a complex with GRP1 in lung. When co-expressed in Chinese hamster ovary cells expressing the human insulin receptor, both proteins display a diffuse, cytoplasmic localization. Acute translocation and co-localization of GRSP1 and GRP1 to ruffles in the plasma membrane was evident after insulin stimulation. These results identify GRSP1 as a novel member of GRP1 signaling complexes that are acutely recruited to plasma membrane ruffles in response to insulin receptor signaling.

ADP-Ribosylation Factors↗

A PPAR gamma-LXR-ABCA1 pathway in macrophages is involved in cholesterol efflux and atherogenesis.

Previous work has implicated PPAR gamma in the regulation of CD36 expression and macrophage uptake of oxidized LDL (oxLDL). We provide evidence here that in addition to lipid uptake, PPAR gamma regulates a pathway of cholesterol efflux. PPAR gamma induces ABCA1 expression and cholesterol removal from macrophages through a transcriptional cascade mediated by the nuclear receptor LXR alpha. Ligand activation of PPAR gamma leads to primary induction of LXR alpha and to coupled induction of ABCA1. Transplantation of PPAR gamma null bone marrow into LDLR -/- mice results in a significant increase in atherosclerosis, consistent with the hypothesis that regulation of LXR alpha and ABCA1 expression is protective in vivo. Thus, we propose that PPAR gamma coordinates a complex physiologic response to oxLDL that involves particle uptake, processing, and cholesterol removal through ABCA1.

ATP Binding Cassette Transporter 1↗