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Biomedical subjects

S Saini

Publications and source records attributed to S Saini.

At least 19 recordsLinked to original sources

A "field change" of inhibited apoptosis occurs in colorectal mucosa adjacent to colorectal adenocarcinoma.

BACKGROUND: Colorectal cancer is associated with a "field change" of increased proliferation throughout the colonic and rectal mucosa. Both proliferation and apoptosis are disrupted during carcinogenesis. Whether altered apoptosis contributes to this field change of microscopic abnormality is, however, unclear. Bcl-xL is an anti-apoptotic protein that inhibits apoptosis by preventing release of cytochrome c, a recognised pathway to cell death. AIM: To determine whether Bcl-xL inhibition of apoptosis is increased in colorectal mucosa adjacent to colorectal adenocarcinoma over that in normal non-neoplastic colorectal mucosa. PATIENTS: PATIENTS undergoing surgical resection for neoplastic (adenocarcinoma) or non-neoplastic disease of the colorectum (rectal prolapse, diverticular disease or volvulus). METHODS: Formalin-fixed, paraffin-wax-embedded surgical colorectal resection specimens were immunostained for Bcl-xL protein. Labelling indices were determined by counting the proportion of positively stained cells in mucosal crypts. RESULTS: 85 patients were studied. Bcl-xL immunostaining was most marked in the upper third of mucosal crypts. It occurred in a minority of samples from non-neoplastic colorectal mucosa, but was seen in most mucosal samples adjacent to colorectal adenocarcinoma. Significant increases (p<0.001) were observed in Bcl-xL labelling indices in the mucosa at 1 cm (n = 46, median labelling index 31.8%, interquartile range 8.3-43.9%) and at 10 cm (n = 52, median labelling index 22.0%, interquartile range 0.0-36.3%) from colorectal carcinoma, compared with normal, non-neoplastic colorectal mucosa (n = 22, median labelling index 0.0%, interquartile range 0.0-0.0%). CONCLUSIONS: The findings are consistent with a field change of inhibited apoptosis in mucosa adjacent to colorectal carcinoma.

Adenocarcinoma↗

Displacement imprinted polymer receptor analysis (DIPRA) for chlorophenolic contaminants in drinking water and packaging materials.

The preparation of a molecularly imprinted polymer (MIP) for pentachlorophenol is described together with two alternative reporter derivatives for use in a displacement imprinted polymer receptor analysis (DIPRA) format procedure. In this procedure, alternative reporter molecules were rebound to the synthetic receptor sites and their displacement by the target analyte was employed as the basis of a simple procedure for the measurement of chlorophenols in water and packaging material samples. Water samples were extracted using the standard procedure (EPA 528) and a detection limit of 0.5 microg l(-1) was achieved using the DIPRA detection method, with good agreement between the displacement technique and GC-ECD analysis. A variety of packaging materials, extracted using a buffered detergent solution were also analysed using the DIPRA procedure and showed good agreement with GC results. In addition, investigation of the cross-reactivity of a range of pesticides and materials commonly encountered in environmental analysis indicated the procedure gave good discrimination between pesticides bearing a chlorophenolic moiety and other materials. The procedure is considered highly suitable for use as a rapid field-test method or for incorporation into a test kit device.

Food Analysis↗

Development of an improved analytical method for the determination of carcinogenic polycyclic aromatic hydrocarbons in transformer oil.

Polynuclear aromatic hydrocarbons (PAHs) are natural constituents of transformer oils and are essential in prolonging transformer in-service lifetime. Issues concerning PAH carcinogenicity demand methods that provide qualitative and quantitative information on the PAH composition of new and in-service oils to allow informed operational decisions to be made. However, current analytical methods focus on PAH fingerprinting, as opposed to quantitative analysis and are also cumbersome, relying on the use of large (>100 ml) volumes of organic solvents, some of which are hazardous. This paper reports a method for the improved quantification of carcinogenic PAHs in transformer oils that is both simple and repeatable. The method uses commercially available solid-phase extraction columns and millilitre volumes of relatively non-hazardous solvents. Extraction efficiencies of > or =74% were obtained for the Environmental Protection Agency priority PAHs. The method has potential for automation and high-throughput analysis and thus is of interest to industries that use transformer oils.

Carcinogens↗

Altered cerebellar functional connectivity mediates potential adaptive plasticity in patients with multiple sclerosis.

BACKGROUND: The cerebellum is of potential interest for understanding adaptive responses in motor control in patients with multiple sclerosis because of the high intrinsic synaptic plasticity of this brain region. OBJECTIVE: To assess the relative roles of interactions between the neocortex and the cerebellum using measures of functional connectivity. METHODS: A role for altered neocortical-cerebellar functional connectivity in adaptive responses to injury from multiple sclerosis was tested using 1.5 T functional magnetic resonance imaging (fMRI) during figure writing with the dominant right hand in patients with predominantly early relapsing-remitting multiple sclerosis. RESULTS: Patients (n = 14) showed a more bihemispheric pattern of activation in motor cortex than healthy controls (n = 11). Correlations between task related signal changes in neocortical and cerebellar regions of interest were used as a measure of functional connectivity. Healthy controls showed strong functional connectivity between the left motor cortex and the right cerebellar dentate nucleus. Significant connectivity between the left primary motor cortex and the right dentate was not found in patients. However, patients had significant connectivity between the left premotor neocortex and the ipsilateral (left) cerebellar cortex (crus I), which was not found in healthy controls. CONCLUSIONS: Changes in apparent cerebellar-neocortical functional connectivity may mediate potentially adaptive changes in brain motor control in patients with multiple sclerosis. Similar changes in the cerebellum and premotor cortex have been reported in the healthy brain during motor learning, suggesting that common mechanisms may contribute to normal motor learning and motor recovery after injury from multiple sclerosis.

Adolescent↗

Pelvic connective tissue resilience decreases with vaginal delivery, menopause and uterine prolapse.

BACKGROUND: The late onset of pelvic visceral prolapse and incontinence after childbirth injury could be explained by menopause-associated connective tissue weakening. Uterosacral ligament resilience (UsR) was assessed to determine whether it influenced uterine or pelvic floor mobility, or varied with age, vaginal delivery, menopause or histological variations in the ligament. METHODS: UsR was measured by tensiometry in ligaments from 85 hysterectomy specimens, and was correlated with the presence of symptomatic uterocervical prolapse, prehysterectomy uterine and anorectal mobility, patient age, history of vaginal delivery and menopause. Forty-five of these ligaments were examined for ligament thickness, muscle to collagen ratio, and oestrogen and progesterone receptor density. The results were correlated with UsR. RESULTS: UsR was significantly reduced (P = 0.02) in symptomatic uterovaginal prolapse, but there was no correlation with either uterocervical or anorectal descent in women without symptomatic prolapse. There was a significant decrease in UsR with vaginal delivery (P = 0.003), menopause (P = 0.009) and older age (P = 0.005). The uterosacral ligament was significantly thinner and contained fewer oestrogen and progesterone receptors after menopause, but this did not affect UsR. CONCLUSION: Where pelvic floor muscles are weakened, decreases in pelvic connective tissue resilience related to the menopause may facilitate progression to symptomatic pelvic visceral prolapse.

Adult↗

Tumour size measurement in an oncology clinical trial: comparison between off-site and on-site measurements.

AIM: To evaluate the degree of variability between lesion measurements obtained by a single observer compared with multiple observers, and in selected cases evaluate which of the two measurements more accurately represented the lesion size. MATERIALS AND METHODS: In this study we compared the performance of a single off-site observer to multiple on-site observers during measurement of 300 abdominal and thoracic lesions. Lesion measurements that were larger than 1cm(2), differed by more than 50%, but by less than 100%, were compared by a single adjudicator, who was blinded to the measurement source (n=46). RESULTS: Measurements of the 300 lesions differed by an average of 109% (SD 251%). Of 266 lesions larger than 1cm(2), results of the single observer compared with multiple observers differed by more than 10% for 249 lesions, more than 30% for 169 lesions, more than 50% for 126 lesions, and more than 100% for 66 lesions. Forty-six lesions were compared by the adjudicator. The adjudicator selected the measurement of the single observer for 37 lesions (80.4%), and the measurement determined by one of the multiple observers for nine lesions (19.6%; p=0.00002). CONCLUSION: Measurement of lesion size by a single observer compared with multiple observers reveals a high degree of variability. An adjudicator selected the measurement of the single observer more frequently than that of multiple observers, with statistical significance. These findings suggest that studies designed to quantify imaging features should limit the number of observers.

Abdominal Neoplasms↗

State-of-the-art imaging of pancreatic neoplasms.

Pancreatic imaging with multidetector CT allows multiphase acquisition of thin slices in a single breath-hold and is especially valuable in obtaining isotropic three-dimensional reformations that improves our ability to provide accurate pre-operative vascular mapping. Advanced MR technology allows faster imaging of pancreas, thus facilitating MR cholangiopancreatography. Use of tissue-specific MR contrast agents, endoscopic ultrasound and PET in pancreatic imaging has evolved considerably. This review article discusses the role of CT, MR, endoscopic ultrasound and PET imaging in pancreas.

Adenocarcinoma↗

Evaluation of germ tube test in various media.

One of the most valuable tests for the rapid presumptive identification of Candida albicans is germ tube production. Previously researchers have concluded superior results with serum in germ tube test. However, handling of pooled human serum has danger of acquisition of hepatitis and HIV infections. Therefore, in the present study we compared various media--pooled human serum, sterile horse serum, peptone water and tryptic soy broth. It was observed that human serum remains to be the best with 100% positivity for identification of C. albicans followed by horse serum (76.3%), peptone water (61.8%) and tryptic soy broth (61.8%).

Candida albicans↗

Effect of manipulation of primary tumour vascularity on metastasis in an adenocarcinoma model.

One explanation for the clinical association between tumour vascularity and probability of metastasis is that increased primary tumour vascularity enhances haematogenous dissemination by offering greater opportunity for tumour cell invasion into the circulation (intravasation). We devised an experimental tumour metastasis model that allowed manipulation of primary tumour vascularity with differential exposure of the primary and metastatic tumour site to angiogenic agents. We used this model to assess the effects of local and systemic increases in the level of the angiogenic agent basic fibroblast growth factor on metastasis. BDIX rats with implanted hind limb K12/TR adenocarcinoma tumours received either intratumoural or systemic, basic fibroblast growth factor or saline infusion. Both intratumoural and systemic basic fibroblast growth factor infusion resulted in significant increases in tumour vascularity, blood flow and growth, but not lung metastasis, compared with saline-infused controls. Raised basic fibroblast growth factor levels and increase in primary tumour vascularity did not increase metastasis. The clinical association between tumour vascularity and metastasis is most likely to arise from a metastatic tumour genotype that links increased tumour vascularity with greater metastatic potential.

Adenocarcinoma↗

Chromodomain protein Swi6-mediated role of DNA polymerase alpha in establishment of silencing in fission Yeast.

Although DNA replication has been thought to play an important role in the silencing of mating type loci in Saccharomyces cerevisiae, recent studies indicate that silencing can be decoupled from replication. In Schizosaccharomyces pombe, mating type silencing is brought about by the trans-acting proteins, namely Swi6, Clr1-Clr4, and Rhp6, in cooperation with the cis-acting silencers. The latter contain an autonomous replication sequence, suggesting that DNA replication may be critical for silencing in S. pombe. To investigate the connection between DNA replication and silencing in S. pombe, we analyzed several temperature-sensitive mutants of DNA polymerase alpha. We find that one such mutant, swi7H4, exhibits silencing defects at mat, centromere, and telomere loci. This effect is independent of the checkpoint and replication defects of the mutant. Interestingly, the extent of the silencing defect in the swi7H4 mutant at the silent mat2 locus is further enhanced in absence of the cis-acting, centromere-proximal silencer. The chromodomain protein Swi6, which is required for silencing and is localized to mat and other heterochromatin loci, interacts with DNA polymerase alpha in vivo and in vitro in wild type cells. However, it does not interact with the mutant pol alpha and is delocalized away from the silent mat loci in the mutant. Our results demonstrate a role of DNA polymerase alpha in the establishment of silencing. We propose a recruitment model for the coupling of DNA replication with the establishment of silencing by the chromodomain protein Swi6, which may be applicable to higher eukaryotes.

Base Sequence↗

Peroxidase enzyme sensor for on-line monitoring of disinfection processes in the food industry.

For desirable environmental reasons, peroxides have replaced halogenated substances for disinfection purposes in the food and beverage industry. However, cost issues and the requirement to remove these agents completely after disinfection necessitate simple, low-cost and sensitive test methods with a wide dynamic range and on-line capability. The development and performance of such a method is detailed here. Low-cost peroxide sensors were fabricated using a single deposition procedure, in which horseradish peroxidase enzyme and dimethylferrocene mediator were entrapped within a cellulose acetate membrane, over the working electrode area of a screen-printed three-electrode assembly. Optimum performance was obtained using HRP and DMFc loadings of 25 U and 0.03 micromol per electrode, respectively, and a mean cellulose acetate molecular weight of 37,000. The device had a detection limit of 49.5 microM hydrogen peroxide and mean RSD values of 21% across the concentration range 49.5-368 microM. In laboratory studies the sensor was shown to have a stability of > or = 4 d in continuous flow-mode maintaining an accuracy of +/- 16% that was considered acceptable for the intended on-line monitoring of the disinfection process. In a field study, it was successfully used on-line within a flow-cell to measure peroxide levels during disinfection of an industrial fermentation vessel.

Biosensing Techniques↗

Dual contrast enhanced magnetic resonance imaging of the liver with superparamagnetic iron oxide followed by gadolinium for lesion detection and characterization.

AIM: Iron oxide contrast agents are useful for lesion detection, and extracellular gadolinium chelates are advocated for lesion characterization. We undertook a study to determine if dual contrast enhanced liver imaging with sequential use of ferumoxides particles and gadolinium (Gd)-DTPA can be performed in the same imaging protocol. MATERIALS AND METHODS: Sixteen patients underwent dual contrast magnetic resonance imaging (MRI) of the liver for evaluation of known/suspected focal lesions which included, metastases (n = 5), hepatocellular carcinoma (HCC;n = 3), cholangiocharcinoma(n = 1) and focal nodular hyperplasia (FNH;n = 3). Pre- and post-iron oxide T1-weighted gradient recalled echo (GRE) and T2-weighted fast spin echo (FSE) sequences were obtained, followed by post-Gd-DTPA (0.1 mmol/kg) multi-phase dynamic T1-weighted out-of-phase GRE imaging. Images were analysed in a blinded fashion by three experts using a three-point scoring system for lesion conspicuity on pre- and post-iron oxide T1 images as well as for reader's confidence in characterizing liver lesions on post Gd-DTPA T1 images. RESULTS: No statistically significant difference in lesion conspicuity was observed on pre- and post-iron oxide T1-GRE images in this small study cohort. The presence of iron oxide did not appreciably diminish image quality of post-gadolinium sequences and did not prevent characterization of liver lesions. CONCLUSION: Our results suggest that characterization of focal liver lesion with Gd-enhanced liver MRI is still possible following iron oxide enhanced imaging.Kubaska, S.et al. (2001). Clinical Radiology, 56, 410-415

Adult↗

MRI contrast agents for evaluating focal hepatic lesions.

Contrast-enhanced magnetic resonance imaging (MRI) has become an important tool in the detection and characterization of focal hepatic lesions especially when other investigations such as ultrasound (US) and computed tomography (CT) are inconclusive. The purpose of this pictorial review is to briefly summarize the properties of various MRI contrast agents used in hepatic imaging and to highlight their role in evaluation of focal hepatic lesions.

Contrast Media↗

Relationship between tumour vascularity and circulating cancer cells in patients with colorectal carcinoma.

BACKGROUND: Colorectal cancer vascularity correlates with risk of metastasis. Greater tumour vascularity may increase haematogenous dissemination by providing a larger vessel area for tumour cell invasion into the circulation. We assessed whether the prevalence of tumour cells in the circulation of colorectal carcinoma patients (CTC) increased with tumour vascularity. METHODS: Pre-operative blood samples were assessed for circulating tumour cells using RT-PCR for carcinoembryonic antigen (CEA) and cytokeratin 20 (CK20) mRNA. Vessel count and volume were morphometrically assessed from tumour biopsies after vasculature staining. RESULTS: Thirty-three colorectal cancer patients (M:F, 20:13; mean age 66 years, SD 11 years) were studied. One or more blood samples were RT-PCR positive for either CEA or CK20 mRNA or both, in 28 (85%) patients. There were no significant differences in the prevalence of RT-PCR positive patients between high and low tumour vascularity groups, or in tumour vessel counts or volume in RT-PCR positive compared with negative patients. CONCLUSIONS: These results do not support vascularity related variation in access of tumour cells to the circulation as an explanation for the correlation between tumour vasculature and metastasis. Tumour vascularity and metastatic potential may be linked phenotypes rather than cause and effect.

Aged↗