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Biomedical subjects

A Aslam

Publications and source records attributed to A Aslam.

At least 19 recordsLinked to original sources
PubMed2006

Defining the T cell antigen proteome of wasp venom.

BACKGROUND: While modulation of T cell function is believed to be important in the successful acquisition of clinical tolerance during venom immunotherapy, little is known of the role of wasp venom specific T cell antigens. OBJECTIVE: We sought comprehensively to characterize the T cell proteome for wasp venom to facilitate the future development of T cell-based immunotherapeutic approaches. METHODS: Using peripheral blood mononuclear cells from wasp venom-allergic individuals and IL-4 ELISPOT analysis, we characterized T cell responses to whole venom and gel filtration/ion exchange-fractionated venom. Reactive fractions were purified and identified using highly sensitive electrospray ion-trap mass spectrometry. RESULTS: Wasp venom-allergic individuals have detectable whole wasp venom-specific T cells directly ex vivo, which show rapid IL-4 effector function. T cell responses to gel filtration/ion exchange fractionated venom were dominated by responses to phospholipase A(1), hyaluronidase and antigen 5. CONCLUSION: Although it is likely that there are many T cell antigens within wasp venom, the main responses are to proteins coincident with the known IgE-binding proteins.

Adult↗
PubMed2006

P53-dependent radiosensitizing effects of Hsp90 inhibitor 17-allylamino-17-demethoxygeldanamycin on human oral squamous cell carcinoma cell lines.

Development of new molecular target therapeutic agents is expected to improve clinical outcome, ideally with efficacy in both single and combined treatment modalities. Because of the potential for affecting multiple signaling pathways, inhibition of the molecular chaperone heat shock protein 90 (Hsp90) may provide a strategy for enhancing tumor cell radiation sensitivity. Therefore, we have investigated the effects of Hsp90 inhibitor 17-Allylamino-17-demethoxygeldanamycin (17-AAG) on radiation sensitivity of human tumor cells in vitro. We evaluated the effects of 17-AAG using oral squamous cell carcinoma (OSCC) cell lines (HSC2, HSC3 and HSC4), including two types of SAS cells with a wild-type (SAS/neo), or a mutated p53 status (SAS/Trp248). Apoptosis and clonogenic survival were examined after exposure of the cells to radiation. For mechanistic insight, we analyzed cell cycle, several signaling factors and molecular markers including Akt, Raf-1, p38 MAPK, Cdc25B, Cdc25C, Cdk2 and p21. Treatment of OSCC cell lines with 17-AAG resulted in cytotoxicity and, when combined with radiation, enhanced the radiation response. However, the responses depended on p53 status. 17-AAG enhanced the radiation sensitivity significantly and induced apoptosis in the SAS/neo cell which has a wild-type p53. But the radiation sensitizing effect of 17-AAG was limited in the SAS/Trp248 cell which has a mutated p53. We also measured the total levels of several prosurvival and cell cycle signaling proteins. Akt, Raf-1 and Cdc25C expression were down-regulated in 17-AAG-treated cells. These data indicate that 17-AAG inhibits the proliferation and enhances the radiation sensitivity of human OSCC cells in various levels. However, enhancement of radiation sensitivity by the Hsp90 inhibitor depended on p53 status. Therefore, Hsp90 therapy combined with radiation might synergize with conventional therapies in patients with wild-type p53.

Apoptosis↗
PubMed2004

Vitamin E deficiency induced neurological disease in common variable immunodeficiency: two cases and a review of the literature of vitamin E deficiency.

Vitamin E deficiency causes a neurological disorder characterised by sensory loss, ataxia and retinitis pigmentosa due to free radical mediated neuronal damage. Symptomatic vitamin E deficiency has been reported in genetic defects of the vitamin E transport protein and in malabsorption complicating cholestasis, abetalipoproteinaemia, celiac disease, cystic fibrosis and small bowel resection. There are no reports to date of vitamin E deficiency in patients with primary immunodeficiencies. We describe two CVID patients with the associated enteropathy who developed neurological disease because of vitamin E deficiency, suggesting a possible predisposition to developing this complication. We recommend that all CVID patients with evidence of an enteropathy be screened for vitamin E deficiency, as early detection and consequent treatment may prevent, halt or reverse the neurological sequelae.

Adult↗
PubMed2003

Traumatic abdominal wall hernia: an unusual bicycle handlebar injury.

Traumatic hernia of the abdominal wall is rare. The mechanism of injury can be severe such as a motor vehicle accident or relatively minor such as a fall onto a bicycle handlebar. In children traumatic abdominal wall hernia can occur even after relatively minor trauma and these cases typically have no associated intra-abdominal injury. We report a traumatic hernia of the anterior abdominal wall in a 7-year-old boy following a fall from a bicycle. A review of the literature revealed only nine similar reports. The presence of localised pain, bruising, and a reducible swelling or a cough impulse suggests the diagnosis. Primary repair with prosthetic material is the preferred treatment.

Abdominal Injuries↗
PubMed2003

Audit of the clinical usefulness of a rapid qualitative ELISA screen for antimyeloperoxidase and antiproteinase 3 antibodies in the assessment of patients with suspected vasculitis.

BACKGROUND: The need for urgent antineutrophil cytoplasmic antibody (ANCA) results when assessing patients with acute renal failure, pulmonary renal syndrome, or mononeuritis multiplex has led to the development of a rapid qualitative ELISA screening assay for antibodies to myeloperoxidase (MPO) and proteinase 3 (PR3). AIMS: To report the use of a rapid qualitative ELISA screen for PR3-ANCA and MPO-ANCA in a regional immunology laboratory and its correlation with standard indirect immunofluorescence (IIF) and quantitative ELISA for PR3-ANCA and MPO-ANCA. METHODS: Over 12 months, 103 samples requiring urgent ANCA testing were screened by a rapid qualitative ELISA and the results compared with IIF and quantitative ELISA assays for PR3-ANCA and MPO-ANCA. RESULTS: There was an excellent correlation between the rapid qualitative ELISA and standard ANCA IIF and a routine ELISA for MPO/PR3-ANCA, with sensitivities ranging from 82% to 100%. There were two false negatives, which gave weak to moderately positive values as determined by routine ELISA. However, the clinical relevance of these two cases is doubtful. CONCLUSIONS: The rapid ELISA for anti-MPO and anti-PR3 correlates well with quantitative ELISA and IIF ANCA, and urgent management decisions in patients with suspected small vessel vasculitis can be based with confidence on this test.

Antibodies, Antineutrophil Cytoplasmic↗
PubMed2000

A new core suture technique for flexor tendon repair: biomechanical analysis of tensile strength and gap formation.

The purpose of this study was to test in vitro a new flexor tendon suture technique that has been developed to withstand the in vivo forces of active tendon motion. This new core suture technique involves locking loops in the form of a cross stitch. The new technique was tested for ultimate tensile strength and gap formation in cadaver human flexor tendons on a tensile testing machine. The new technique proved significantly stronger than the modified Kessler core suture.

Cadaver↗
PubMed1999

Histochemical and genetic analysis of colonic mucin glycoproteins in Hirschsprung's disease.

BACKGROUND/PURPOSE: Mucin glycoproteins (mucins) recently have been shown to be deficient in the colonic mucosa of patients with Hirschsprung's disease (HD). The authors performed a detailed histo- and immunohistochemical analysis of mucins in the colonic mucosa and studied the expression of mucin genes to characterize histologically mucin quality and gene expression in HD compared with controls. METHODS: Paraffin-embedded 4-microm thick sections from patients with HD (n = 11 ganglionic, 10 aganglionic) and controls (n = 19) were taken. Slides were stained with mild periodic acid Schiff with and without saponification with KOH (reacts with O-actylated mucins), high iron diamine/alcian blue (differentiates sulphated v nonsulphated mucins), the monoclonal antimucin antibodies, PR3A5 (against di- and tri-O-acetylated sialic acids) and 91.9H (against sulphated mucins). O-acetylation and sulphation both confer an increased resistance of mucins to bacterial degradation and are thought to be important in the defensive function of the colonic mucus gel layer. In situ hybridization was used to study expression of the mucin genes MUC 1, 2, 3, 4, 5AC, 5B, 6, 7, and 8. [35S]-sulphate-labelled antisense oligonucleotide 48mer probes designed to the known tandem repeat domains of MUC genes were used. After hybridization and washing the slides were opposed to Hyperfilm MP for 7 days. The autoradiographs were scored by three independent observers for differences in expression and by image analysis. Those with positive findings were dipped in photographic emulsion, developed, and counterstained for photomicrographs. RESULTS: There were different patterns of staining dependent on the region of the colon and especially the age of the patient with three reagents. No significant differences in the histological staining pattern was detected between HD patients and controls. The colonic mucins in HD were found to be primarily O-acetylated and sulphated. The MUC gene expression was similar in patients and controls. MUC2 and 4 were strongly expressed, MUC1, 3, and 5B had moderate to weak expression, and MUC 5AB, 6, 7, and 8 had baseline expression. CONCLUSIONS: The mucin glycoproteins in children with HD, although quantitatively deficient, show no qualitative differences on histo- and immunohistochemical staining from normal controls. The expression of all the known mucin genes, the genetic control of mucin secretion, and the quality of mucins, is similar to normal controls.

Age Factors↗
PubMed1998

The role of magnetic resonance imaging in the preoperative assessment of anorectal anomalies.

The role of magnetic resonance imaging (MRI) compared to other investigations in providing information relevant to and affecting surgical management in patients with anorectal anomalies (ARA) was studied in two groups of patients. In group 1 a pilot study was done in 9 patients with colostomy for high ARA awaiting posterior sagittal anorectoplasty. These patients had MRI, plain radiographs, a distal loopogram through the mucous fistula, ultrasound scans of the spinal cord and urinary tract, and a micturating cystourethrogram. The level of bowel and spinal-cord termination was correctly determined in all patients by MRI and conventional investigations. The presence or absence of a fistula, urological abnormalities, and bony abnormalities of the pelvis and spine were better visualized by conventional investigations than with MRI. The striated-muscle complex (SMC) was well-visualized by MRI, the thickness accurately graded, and the findings confirmed at operation. The information on muscle thickness and the presence or absence of a fistula was interesting, but played no part in decisions made about surgical management, and the operative technique was not altered. In group 2 the patients were much older and had MRI for persistent problems, mainly soiling; 6 had low lesions and 6 had high lesions. Three patients with low lesions were found to have intraspinal abnormalities on MRI; 4 were found to have malpositioned bowel in the SMC, which was again accurately visualized and graded. Therefore, in 7/12 patients of this group a surgically correctable abnormality was found. We conclude that MRI has no role as a primary investigation in patients with high ARA, but it is useful if there are suspected spinal-cord problems or persistent problems after definitive surgery.

Anal Canal↗
PubMed1998

Turnover of radioactive mucin precursors in the colon of patients with Hirschsprung's disease correlates with the development of enterocolitis.

BACKGROUND/PURPOSE: Mucin glycoproteins (mucins) in the colonic mucus gel layer interact with pathogens performing protective functions by a variety of mechanisms. It is recognised that patients with Hirschsprung's disease (HD) are prone to episodes of enterocolitis even after corrective surgery, the aetiology of which is poorly understood. The authors correlated the turnover of radioactive mucin precursors in organ culture of the proximal ganglionated colon at the time of pull-through with the development of postoperative enterocolitis. METHODS: The colonic mucins in the retained proximal ganglionated colon of nine HD patients at the time of pull-through were studied. Organ culture of intact mucosa was performed with radioactive mucin precursors 35S-sulphate and 3H-glucosamine. Mucins in the secretions and epithelial cells were then purified by gel filtration. Turnover of the isotopes was determined by relating radioactivity to tissue DNA content. These patients were followed up prospectively for a mean duration of 30.8 months. The patients were assigned to one of two groups according to the criteria of requiring hospital admission for enterocolitis during this period. There were five patients in the group that remained well after corrective surgery and four in the group that developed entercolitis. The turnover values of both radioisotopes were analysed for differences in the two groups of patients. RESULTS: Patients in the enterocolitis group had a median value for turnover of 331 dpm/microg DNA, and the group that was well had a median value of 2044 dpm/microg DNA. These differences were statistically significant (Mann-Whitney, P = .037). CONCLUSIONS: A reduced turnover of mucins as shown by incorporation of radioactive precursors will give rise to a defective colonic mucus-defensive barrier. It can be inferred that the lower the turnover, the more prone a patient is to postoperative enterocolitis. It is therefore possible that organ culture with radioactive mucin precursors of the proximal ganglionated mucosa performed at the time of pull-through has a predictive value in the development of postoperative enterocolitis.

Colon↗
PubMed1997

Children with Hirschsprung's disease have an abnormal colonic mucus defensive barrier independent of the bowel innervation status.

The mucus gel layer in the colon plays an important role in the defensive mechanisms against pathogenic organisms. Mucin glycoproteins or mucins are the major component of this gel. We studied the mucins in patients who had Hirschsprung's disease (HD) by colonic mucosal organ culture with radioactive mucin precursors [35S]-sulphate and [3H]-glucosamine. The secreted and cellular mucus fractions were collected after 24-hour incubation, and mucins were purified by gel filtration. The ratio of incorporation of the precursors and their turnover were quantified. Purified mucins were tested against wheat germ agglutinin for total mucin turnover. We used nine aganglionic bowel samples, 10 ganglionic bowel samples from HD patients, and 13 age-matched normal controls. There were no significant differences in the three groups in ratio of incorporation. The turnover with both radioactive precursors was reduced in both aganglionic and ganglionic bowel of HD, these differences were significant in [35S]-sulphate incorporation in the cellular fraction, ganglionic bowel being most affected. Total mucin turnover, as assessed by reactivity with wheat germ aggultinin, was reduced in both HD groups, being significant in the cellular fraction, aganglionic bowel being the most affected. These results signify an abnormal mucus defensive barrier in the colon of HD patients, even in the ganglionic bowel, which is thought to be normal and is retained at the definitive pull-through operation. This abnormality may be an etiological factor in the pathogenesis of enterocolitis of HD.

Chromatography, Gel↗