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Biomedical subjects

S Patel

Publications and source records attributed to S Patel.

At least 19 recordsLinked to original sources
PubMed2006

Covalent antithrombin-heparin complexes.

Unfractionated heparin (UFH) and low molecular weight heparin (LMWH) have been utilized as primary anticoagulants for thrombosis prophylaxis and treatment. However, a number of biophysical and safety limitations have led to development of new anticoagulants. Covalent antithrombin-heparin (ATH) complexes may address many of these issues. Early ATH products were prepared that had increased intravenous half-lives relative to UFH but lacked any improvement in anti-factor Xa activity or had no catalytic activity or reactivity against thrombin. However, a recent conjugate developed by Chan et al. has displayed a number of superior properties. Chan et al. ATH has an increased direct thrombin inhibition rate and can catalyze coagulant enzyme inhibition by exogenous antithrombin with very high specific activity. Unlike UFH, clot-bound thrombin is readily inhibited by ATH and, at similar antithrombotic efficacy, the ATH has improved bleeding profiles compared to heparins. Given the preclinical findings, Chan et al. ATH may warrant clinical trial testing for control of clot propagation.

Animals↗
PubMed2006

Pancreatic cancer cells overexpress gelsolin family-capping proteins, which contribute to their cell motility.

BACKGROUND: Previously, proteomic methods were applied to characterise differentially expressed proteins in microdissected pancreatic ductal adenocarcinoma cells. AIMS: To report that CapG and a related protein, gelsolin, which have established roles in cell motility, are overexpressed in metastatic pancreatic cancer; and to describe their pattern of expression in pancreatic cancer tissue and their effect on cell motility in pancreatic cancer cell lines. METHODS: CapG was identified by mass spectrometry and immunoblotting. CapG and gelsolin expression was assessed by immunohistochemical analysis on a pancreatic cancer tissue microarray and correlated with clinical and pathological parameters. CapG and gelsolin levels were reduced using RNA interface in Suit-2, Panc-1 and MiaPaCa-2 cells. Cell motility was assessed using modified Boyden chamber or wound-healing assays. RESULTS: Multiple isoforms of CapG were detected in pancreatic cancer tissue and cell lines. Immunohistochemical analysis of benign (n = 44 patients) and malignant (n = 69) pancreatic ductal cells showed significantly higher CapG staining intensity in nuclear (p<0.001) and cytoplasmic (p<0.001) compartments of malignant cells. Similarly, gelsolin immunostaining of benign (n = 24 patients) and malignant (n = 68 patients) pancreatic ductal cells showed higher expression in both compartments (both p<0.001). High nuclear CapG was associated with increased tumour size (p = 0.001). High nuclear gelsolin was associated with reduced survival (p = 0.01). Reduction of CapG or gelsolin expression in cell lines by RNAi was accompanied by significantly impaired motility. CONCLUSIONS: Up regulation of these actin-capping proteins in pancreatic cancer and their ability to modulate cell motility in vitro suggest their potentially important role in pancreatic cancer cell motility and consequently dissemination.

Adenocarcinoma↗
PubMed2006

Attentional performance of C57BL/6 and DBA/2 mice in the 5-choice serial reaction time task.

C57BL/6 and DBA/2 were compared in the 5-choice serial reaction time task for differences in performance related to attention and impulsivity. The goal was to examine behavioural processes in mice that may relate to ADHD in humans. Groups of male mice were trained to nose-poke in response to a stimulus light presented randomly in one of five holes; correct responses were reinforced with food. During training the stimulus duration (SD) was reduced progressively from 60 to 0.5s. The C57BL/6 and DBA/2 mice did not differ during early stages of training when attentional demands were low (SD of 60, 10 or 5s). As task demands increased, strain differences emerged; C57BL/6 mice were more accurate than DBA/2 mice with stimuli of 2, 1 and 0.5s. DBA/2 mice also made more anticipatory (impulsive) responses during inter-trial intervals than C57BL/6 mice at SD of 5, 2, 1 and 0.5s. The ability to carry out the task was present in both strains of mice but they differed significantly in the levels of performance that were achieved. It is argued that the differences in accuracy and anticipatory responding were closely related and that the primary difference between the strains may be in impulsivity.

Analysis of Variance↗
PubMed2006

Common variations in the ALMS1 gene do not contribute to susceptibility to type 2 diabetes in a large white UK population.

AIMS/HYPOTHESIS: Alström syndrome is a rare monogenic disorder characterised by retinal dystrophy, deafness and obesity. Patients also have insulin resistance, central obesity and dyslipidaemia, thus showing similarities with type 2 diabetes. Rare mutations in the ALMS1 gene cause severe gene disruption in Alström patients; however, ALMS1 gene polymorphisms are common in the general population. The aim of our study was to determine whether common variants in ALMS1 contribute to susceptibility to type 2 diabetes in the UK population. METHODS: Direct sequencing was performed on coding regions and intron/exon boundaries of the ALMS1 gene in 30 unrelated probands with type 2 diabetes. The linkage disequilibrium (LD; D' and r2) and haplotype structure were examined for the identified variants. The common (minor allele frequency [MAF] >5%) single-nucleotide polymorphisms tagging the common haplotypes (tagged SNPs [tSNPs]) were identified and genotyped in 1985 subjects with type 2 diabetes, 2,047 control subjects and 521 families. RESULTS: We identified 18 variants with MAF between 6 and 38%. Three SNPs efficiently tagged three common haplotypes (rs1881245, rs3820700 and rs1320374). There was no association (all p > 0.05) between the tSNPs and type 2 diabetes in the case-control study and minor alleles of the tSNPs were not overtransmitted to probands with type 2 diabetes in the family study. CONCLUSIONS/INTERPRETATION: Common variations in the ALMS1 gene were not associated with type 2 diabetes in a large study of a white UK population.

Adult↗
PubMed2006

Administration of kisspeptin-54 into discrete regions of the hypothalamus potently increases plasma luteinising hormone and testosterone in male adult rats.

Kisspeptin-54 is the peptide product of the KiSS-1 gene and an endogenous agonist of the GPR54 receptor. KiSS-1 was initially discovered as a metastasis suppressor gene, but recent studies demonstrate that the kisspeptin/GPR54 system is a key regulator of the reproductive system. Disrupted GPR54 signalling causes hypogonadotrophic hypogonadism in rodents and man. Intracerebroventricular or peripheral administration of kisspeptin potently stimulates the hypothalamic-pituitary-gonadal (HPG) axis via the hypothalamic gonadotrophin-releasing hormone system. We have investigated the effect of injection of kisspeptin-54 into discrete hypothalamic regions on the HPG axis. To construct a dose-response curve for the effects of intrahypothalamic kisspeptin administration, adult male Wistar rats were cannulated into the medial preoptic area (MPOA) at the level of the organum vasculosum laminae terminalis (OVLT). Kisspeptin-54 was injected into the MPOA at doses of 0.01, 0.1, 1, 10 and 100 pmol. At 60 min following injection of 1, 10 or 100 pmol kisspeptin-54, plasma luteinising hormone (LH) and total testosterone levels were significantly increased. Adult male Wistar rats were then cannulated into the rostral preoptic area at the level of the OVLT (RPOA), the MPOA, the paraventricular (PVN), dorsomedial (DMN) and arcuate hypothalamic nuclei, and the lateral hypothalamic area. A dose of 1 pmol kisspeptin-54 was administered into all areas. The circulating levels of LH and total testosterone were significantly increased 60 min postinjection of kisspeptin-54 into the RPOA, MPOA, PVN and arcuate nucleus. Our results suggest that kisspeptin may mediate its effects on the HPG axis via these regions of the hypothalamus.

Analysis of Variance↗
PubMed2006

Addiction toxin Fst has unique effects on chromosome segregation and cell division in Enterococcus faecalis and Bacillus subtilis.

The Fst toxin of the Enterococcus faecalis pAD1-encoded par addiction module functions intracellularly to kill plasmid-free segregants. Previous results had shown that Fst induction results in membrane permeabilization and cessation of macromolecular synthesis, but only after 45 min. Electron micrographs of toxin-induced cells showed no obvious membrane abnormalities but did reveal defects in nucleoid segregation and cell division, begging the question of which is the primary effect of Fst. To distinguish the possibilities, division septae and nucleoids were visualized simultaneously with fluorescent vancomycin and a variety of DNA stains. Results showed that division and segregation defects occurred in some cells within 15 min after induction. At these early time points, affected cells remained resistant to membrane-impermeant DNA stains, suggesting that loss of membrane integrity is a secondary effect caused by ongoing division and/or segregation defects. Fst-resistant mutants showed greater variability in cell length and formed multiple septal rings even in the absence of Fst. Fst induction was also toxic to Bacillus subtilis. In this species, Fst induction caused only minor division abnormalities, but all cells showed a condensation of the nucleoid, suggesting that effects on the structure of the chromosomal DNA might be paramount.

Bacillus subtilis↗
PubMed2006

An evaluation of tympanic thermometry in a paediatric emergency department.

BACKGROUND AND OBJECTIVES: The consequences of missing fever in children can be grave. Body temperature is commonly recorded at the axilla but accuracy is a problem. This study aimed to evaluate the accuracy of a tympanic thermometer in the paediatric emergency setting. METHOD: In a total of 106 infants, the body temperature was measured in the daytime with an infrared tympanic thermometer, and at the axilla with an electronic thermometer and at the rectum (gold standard for measurement of body temperature). Fever was defined as a rectal temperature of 38.0 degrees C or greater, axillary temperature of 37.5 degrees C or greater, and tympanic temperature of 37.6 degrees C or greater. The temperature readings at the three sites were compared statistically. RESULTS: There was a greater correlation of the tympanic measurement with the rectal measurement than the axillary with the rectal in both febrile and afebrile infants. The mean difference between the tympanic and rectal measurements was lower than that between the axillary and rectal measurements in both groups of infants (tympanic 0.38 degrees C and 0.42 degrees C, and axillary 1.11 degrees C and 1.58 degrees C, respectively). Tympanic measurements had a sensitivity of 76% whereas axillary measurements had a sensitivity of only 24% with rectal temperatures of 38-38.9 degrees C. CONCLUSION: Tympanic thermometry is more accurate than measurement of temperature with an electronic axillary thermometer. It is also quick and safe, and thus it is recommended in the paediatric emergency setting.

Axilla↗
PubMed2006

An overview of the prevalence of 25-hydroxy-vitamin D inadequacy amongst elderly patients with or without fragility fracture in the United Kingdom.

BACKGROUND: Many studies have investigated the prevalence of 25-hydroxy-vitamin D inadequacy throughout the world and found a high prevalence of 25-hydroxy-vitamin D inadequacy in older patients, particularly those with fragility fracture. SCOPE: To review the findings from vitamin D audits from six units across the UK and compare with previously published data from around the world. Results from four units have been previously published (Belfast, Glasgow, London and Medway) and this paper presents new data from Southampton and Carshalton, and further sub-analysis of the data from Medway. FINDINGS: Three audits of patients attending metabolic bone clinics (Carshalton, Medway and Southampton) identified 954 patients, of which overall 49% had a prior fragility fracture. Mean 25-hydroxy-vitamin D levels ranged from 47.7 nmol/L to 62.4 nmol/L. Of these patients 72.9-88.9% had a 25-hydroxy-vitamin D level < 80 nmol/L, 68.8-83.3% < 70 nmol/L and 37.5-59.1% < 50 nmol/L. The mean age of patients ranged from 60.0 to 67.5 years. Sub-analysis of the data by fracture status revealed that patients with fracture had lower mean levels of 25-hydroxy-vitamin D compared with patients without fracture. This was statistically significant in the sub-analysis of the Medway data (45.3 nmol/L versus 49.9 nmol/L, p < 0.005). Three audits identified 330 patients with fragility fracture. Audits from Glasgow and Belfast specifically identified patients with fragility fracture. A subgroup of patients with fracture aged over 50 years from the Medway audit was also included in this group. Mean levels of 25-hydroxy-vitamin D ranged from 40.0 nmol/L to 52.3 nmol/L. 83.7-96.4% of patients had a 25-hydroxy-vitamin D level < 80 nmol/L, 73.3-89.7% < 70 nmol/L and 55.8-73.2% < 50 nmol/L. The mean age of patients ranged from 65.3 to 68.6 years. The audits carried out in Belfast and Medway were also divided by supplementation status. Mean 25-hydroxy-vitamin D levels were 48.1 nmol/L in Belfast and 40.5 nmol/L in Medway in the patients not receiving supplements and 53.8 nmol/L and 59.9 nmol/L, respectively in the patients receiving supplements. The difference was statistically significant in the Medway audit (p < 0.0001), but not in the smaller Belfast audit (p = 0.216). As would be expected, the prevalence of 25-hydroxy-vitamin D inadequacy was higher in the patients not receiving supplements, for example at the 70 nmol/L threshold: 82.6% versus 67.1% in Belfast and 89.6% versus 72.7% in Medway. Three audits specifically identified 694 patients with hip fracture (Belfast, Glasgow and London). Mean levels of 25-hydroxy-vitamin D ranged from 24.7 nmol/L to 36.1 nmol/L. Of these patients 90.7-99.0% had a 25-hydroxy-vitamin D level < 80 nmol/L, 88.4-98.0% < 70 nmol/L and 81.6-92.7% < 50 nmol/L. The mean age of patients ranged from 73.4 to 80.5 years. CONCLUSION: Inadequate 25-hydroxy-vitamin D levels are extremely common in the elderly and particularly so in patients with fragility fracture - specifically in those with hip fracture. Although the differing audit specifications and assay techniques used make direct comparisons difficult, the data do provide a snapshot of 25-hydroxy-vitamin D status across the UK and are consistent with those previously observed elsewhere in Europe and the rest of the world.

Aged↗
PubMed2006

Contribution of genomics and proteomics in understanding the role of modifying factors in Parkinson's disease.

Parkinson's disease (PD) is a complex neurological disorder, characterized by selective degeneration of nigrostriatal dopaminergic neurons. It is a multi-factorial disease, contributed by a combination of age, genetic and environmental factors. Etiology of sporadic PD and mechanism underlying selective loss of dopaminergic neurons has not yet been clearly understood. Recent developments in genomics and proteomics have revolutionized the research on PD at genetic level. Differential gene expression patterns (DNA biochip technology), age-dependent complex genetic patterns (SNP genotyping), and protein expression profiles (proteomics) of PD patients have started providing the specific and rigorous molecular explanation and role of modifying factors in PD. Genomics and proteomics are further expected to help in developing biomarkers for diagnosis of early onset PD and also to develop valuable and potential therapeutic strategies for its treatment. In this review, we have discussed the progress made by genomics and proteomics, in understanding the role of modifying factors in PD.

Animals↗
PubMed2005

Nitric oxide synthase localization in the rat neutrophils: immunocytochemical, molecular, and biochemical studies.

Nitric oxide (NO) modulates diverse functions of polymorphonuclear neutrophils (PMNs), but localization of NO synthase (NOS) and identification of its interacting proteins remain the least defined. The present study discerns subcellular distribution of NOS and caveolin-1, a prominent NOS-interacting protein in rat PMNs. Localization of NOS was explored by confocal and immunogold electron microscopy, and its activity was assessed by L-[3H] arginine and 4,5-diaminofluorescein diacetate (DAF-2DA). Reverse transcriptase-polymerase chain reaction using NOS primers and Western blotting demonstrated the presence of neuronal NOS (nNOS) and inducible NOS (iNOS) in PMNs. Immunocytochemical studies exhibited distribution of nNOS and iNOS in cytoplasm and nucleus, and L-[3H] citrulline formation and DAF fluorescence confirmed NOS activity in both fractions. NOS activity correlated positively with calmodulin concentration in both of the fractions. nNOS and iNOS colocalized with caveolin-1, as evidenced by immunocytochemical and immunoprecipitation studies. The results thus provide first evidence of nNOS and iNOS in the nuclear compartment and suggest NOS interaction with caveolin-1 in rat PMNs.

Animals↗
PubMed2005

An origin for short gamma-ray bursts unassociated with current star formation.

Two short (< 2 s) gamma-ray bursts (GRBs) have recently been localized and fading afterglow counterparts detected. The combination of these two results left unclear the nature of the host galaxies of the bursts, because one was a star-forming dwarf, while the other was probably an elliptical galaxy. Here we report the X-ray localization of a short burst (GRB 050724) with unusual gamma-ray and X-ray properties. The X-ray afterglow lies off the centre of an elliptical galaxy at a redshift of z = 0.258 (ref. 5), coincident with the position determined by ground-based optical and radio observations. The low level of star formation typical for elliptical galaxies makes it unlikely that the burst originated in a supernova explosion. A supernova origin was also ruled out for GRB 050709 (refs 3, 31), even though that burst took place in a galaxy with current star formation. The isotropic energy for the short bursts is 2-3 orders of magnitude lower than that for the long bursts. Our results therefore suggest that an alternative source of bursts--the coalescence of binary systems of neutron stars or a neutron star-black hole pair--are the progenitors of short bursts.

Journal Article↗
PubMed2005

Is herniography useful?

Herniography has been used for 25 years in the diagnosis of occult herniation but has not gained widespread acceptance in the UK, despite studies confirming its high sensitivity and specificity for occult hernias and an excellent record of safety and patient acceptability. The traditional approach in the UK to suspected occult groin herniation has been surgical exploration. This study examined the use of herniography in a single district general hospital to assess its impact in limiting unnecessary groin explorations and allowing discharge of patients without hernias. The case notes of 90 successive patients referred for herniography by the department of general surgery in a single UK district general hospital over an 18-month period were reviewed. Eighty-seven completed examinations were analysed in which 23 hernias were diagnosed in 20 patients. Thirteen patients have undergone hernia repair with resolution of symptoms. There were no false positive examinations, although two inguinal hernias were incorrectly diagnosed radiologically as femoral hernias; there were two false negative examinations where additional hernias were found at laparoscopic repair. There were no reported complications. Twenty-four patients were discharged directly from the surgical clinic after a negative herniogram. Thirty patients were referred to other specialities. No patient had undergone groin exploration after a negative herniogram. Herniography is a useful tool in assessing obscure groin pain and potential occult herniation. It can reliably rule out the presence of a hernia and avoid the need for surgical exploration. Many patients with a negative herniogram can be reassured and discharged, whilst others may be referred on to other specialities safe in the knowledge that an occult hernia has been excluded.

Adult↗
PubMed2005

Acute tonsillitis: an unusual presentation of Kawasaki syndrome: a case report and review of the literature.

Kawasaki syndrome is an acute, self-limiting vasculitis that occurs mainly in children. The disorder is difficult to diagnose, a problem compounded by the lack of a specific diagnostic test. If the condition is unrecognised or treated sub-optimally, there is a 25% risk of developing serious cardiovascular complications. We report the case of an 8-year-old boy presenting with a history of acute tonsillitis and cervical lymphadenopathy in which the diagnosis of Kawasaki syndrome became apparent 4 days after admission. The case emphasises the importance of having a high index of suspicion for Kawasaki syndrome in children presenting with tonsillitis and cervical lymphadenopathy who do not respond to antibiotics or who have atypical features at the time of or after admission. A literature review of previous cases reveals a higher than usual age of presentation for the disease that could result in a greater percentage of cardiac complications.

Acute Disease↗