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1.
Nat Commun ; 13(1): 5863, 2022 Oct 04.
Article in English | MEDLINE | ID: mdl-36195621

ABSTRACT

Quasi-particles are elementary excitations of condensed matter quantum phases. Demonstrating that they keep quantum coherence while propagating is a fundamental issue for their manipulation for quantum information tasks. Here, we consider anyons, the fractionally charged quasi-particles of the Fractional Quantum Hall Effect occurring in two-dimensional electronic conductors in high magnetic fields. They obey anyonic statistics, intermediate between fermionic and bosonic. Surprisingly, anyons show large quantum coherence when transmitted through the localized states of electronic Fabry-Pérot interferometers, but almost no quantum interference when transmitted via the propagating states of Mach-Zehnder interferometers. Here, using a novel interferometric approach, we demonstrate that anyons do keep quantum coherence while propagating. Performing two-particle time-domain interference measurements sensitive to the two-particle Hanbury Brown Twiss phase, we find 53 and 60% visibilities for anyons with charges e/5 and e/3. Our results give a positive message for the challenge of performing controlled quantum coherent braiding of anyons.

2.
J Hazard Mater ; 418: 126219, 2021 09 15.
Article in English | MEDLINE | ID: mdl-34102370

ABSTRACT

Extensive use of nanomaterials in agriculture will inevitably lead to their release to the environment in significant loads. Thus, understanding the fate of nanoparticles in the soil-plant environment, and potential presence and consequent implication of nanoparticles in food and feed products, is required. We study plant uptake of gold nanoparticles from soil, and their distribution, translocation and speciation (in terms of particle size change and release of ionic Au) in the different plant tissues of four important crops (potato, radish, carrot and lettuce). Our new analytical protocol and experiments show the feasibility of determining the presence, concentration and distribution of nanoparticles in different plant parts, which differ from plant to plant. Critically, we identify the evident capacity of plants to break down (or substantially change the properties of) nanoparticles in the rhizosphere prior to uptake, as well as the evident capacity of plants to reorganize ionic metals as nanoparticles in their tissues. This could lead to nanoparticle exposure through consumption of crops.


Subject(s)
Daucus carota , Metal Nanoparticles , Nanoparticles , Raphanus , Soil Pollutants , Solanum tuberosum , Gold , Lactuca , Plant Roots/chemistry , Soil Pollutants/analysis
3.
Ann R Coll Surg Engl ; 101(8): 609-616, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31508984

ABSTRACT

INTRODUCTION: Hypothermic machine perfusion, an organ preservation modality, involves flow of chilled preservation fluid through an allograft's vasculature. This study describes a simple, reproducible, human model that allows for interrogation of flow effects during ex vivo organ perfusion. MATERIALS AND METHODS: Gonadal veins from deceased human renal allografts were subjected to either static cold storage or hypothermic machine perfusion for up to 24 hours. Caspase-3, Krüppel-like factor 2 expression and electron microscopic analysis were compared between 'flow' and 'no-flow' conditions, with living donor gonadal vein sections serving as negative controls. RESULTS: The increase in caspase-3 expression was less pronounced for hypothermic machine-perfused veins compared with static cold storage (median-fold increase 1.2 vs 2.3; P < 0.05). Transmission electron microscopy provided ultrastructural corroboration of endothelial cell apoptosis in static cold storage conditions. For static cold storage preserved veins, Krüppel-like factor 2 expression diminished in a time-dependent manner between baseline and 12 hours (P < 0.05) but was abrogated and reversed by hypothermic machine perfusion (P < 0.05). CONCLUSIONS: Our methodology is a simple, reproducible and successful model of ex vivo perfusion in the context of human organ preservation. To demonstrate the model's utility, we establish that two widely used markers of endothelial health (caspase-3 and Krüppel-like factor 2) differ between the flow and no-flow conditions of the two predominant kidney preservation modalities. These findings suggest that ex vivo perfusion may mediate the induction of a biochemically favourable endothelial niche which may contribute tohypothermic machine perfusion's association with improved renal transplantation outcomes.


Subject(s)
Kidney Transplantation/methods , Kidney/blood supply , Models, Biological , Organ Preservation Solutions/pharmacokinetics , Organ Preservation/methods , Apoptosis , Biomarkers/metabolism , Cadaver , Caspase 3/metabolism , Cold Temperature , Endothelium, Vascular/metabolism , Humans , Kidney/metabolism , Kidney/ultrastructure , Kruppel-Like Transcription Factors/metabolism , Microscopy, Electron , Perfusion/methods , Veins/metabolism , Veins/ultrastructure
4.
Diabet Med ; 34(8): 1067-1073, 2017 08.
Article in English | MEDLINE | ID: mdl-28510327

ABSTRACT

AIM: To investigate whether people with diabetes have an elevated risk of kidney allograft rejection in a well characterized clinical cohort in the setting of contemporary immunosuppression. METHODS: We conducted a retrospective cohort study including all kidney allograft recipients at a single centre between 2007 and 2015, linking clinical, biochemical and histopathological data from electronic patient records. RESULTS: Data were analysed for 1140 kidney transplant recipients. The median follow-up was 4.4 years post-transplantation, and 117 of the kidney transplant recipients (10.2%) had diabetes at time of transplantation. Kidney allograft recipients with vs without diabetes were older (53 vs 45 years; P<0.001) and more likely to be non-white (41.0% vs 26.4%; P=0.001). Kidney allograft recipients with vs without diabetes had a higher risk of cellular rejection (19.7% vs 12.4%; P=0.024), but not of antibody-mediated rejection (3.4% vs 3.7%; P=0.564). Graft function and risk of death-censored graft loss were similar in the two groups, but kidney allograft recipients with diabetes had a higher risk of death and overall graft loss than those without diabetes. In a Cox regression model of non-modifiable risk factors at time of transplantation, diabetes was found to be an independent risk factor for cellular rejection (hazard ratio 1.445, 95% CI 1.023-1.945; P=0.042). CONCLUSIONS: Kidney allograft recipients with diabetes at transplantation should be counselled regarding their increased risk of cellular rejection but reassured regarding the lack of any adverse impact on short-to-medium term allograft function or survival.


Subject(s)
Diabetic Nephropathies/surgery , Graft Rejection/complications , Kidney Failure, Chronic/surgery , Kidney Transplantation/adverse effects , Adult , Age Factors , Cohort Studies , Combined Modality Therapy/adverse effects , Diabetic Nephropathies/complications , Diabetic Nephropathies/immunology , Diabetic Nephropathies/therapy , Disease-Free Survival , England/epidemiology , Female , Follow-Up Studies , Graft Rejection/epidemiology , Graft Rejection/immunology , Graft Rejection/prevention & control , Hospitals, Teaching , Humans , Immunosuppression Therapy/adverse effects , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/immunology , Kidney Failure, Chronic/therapy , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Risk Factors
5.
AJNR Am J Neuroradiol ; 38(5): 923-927, 2017 May.
Article in English | MEDLINE | ID: mdl-28364006

ABSTRACT

BACKGROUND AND PURPOSE: The detection of new subtle brain pathology on MR imaging is a time-consuming and error-prone task for the radiologist. This article introduces and evaluates an image-registration and subtraction method for highlighting small changes in the brain with a view to minimizing the risk of missed pathology and reducing fatigue. MATERIALS AND METHODS: We present a fully automated algorithm for highlighting subtle changes between multiple serially acquired brain MR images with a novel approach to registration and MR imaging bias field correction. The method was evaluated for the detection of new lesions in 77 patients undergoing cardiac surgery, by using pairs of fluid-attenuated inversion recovery MR images acquired 1-2 weeks before the operation and 6-8 weeks postoperatively. Three radiologists reviewed the images. RESULTS: On the basis of qualitative comparison of pre- and postsurgery FLAIR images, radiologists identified 37 new ischemic lesions in 22 patients. When these images were accompanied by a subtraction image, 46 new ischemic lesions were identified in 26 patients. After we accounted for interpatient and interradiologist variability using a multilevel statistical model, the likelihood of detecting a lesion was 2.59 (95% CI, 1.18-5.67) times greater when aided by the subtraction algorithm (P = .017). Radiologists also reviewed the images significantly faster (P < .001) by using the subtraction image (mean, 42 seconds; 95% CI, 29-60 seconds) than through qualitative assessment alone (mean, 66 seconds; 95% CI, 46-96 seconds). CONCLUSIONS: Use of this new subtraction algorithm would result in considerable savings in the time required to review images and in improved sensitivity to subtle focal pathology.


Subject(s)
Algorithms , Brain Diseases/diagnostic imaging , Image Interpretation, Computer-Assisted/methods , Magnetic Resonance Imaging/methods , Subtraction Technique , Aged , Brain Diseases/pathology , Female , Humans , Male , Middle Aged , Sensitivity and Specificity
6.
Br J Surg ; 103(9): 1230-6, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27245933

ABSTRACT

BACKGROUND: The aim of the present study was to determine the effects of cold ischaemia time (CIT) on living donor kidney transplant recipients in a large national data set. METHODS: Data from the National Health Service Blood and Transplant and UK Renal Registry databases for all patients receiving a living donor kidney transplant in the UK between January 2001 and December 2014 were analysed. Patients were divided into three groups depending on CIT (less than 2 h, 2-4 h, 4-8 h). Risk-adjusted outcomes were assessed by multivariable analysis adjusting for discordance in both donor and recipient characteristics. RESULTS: Outcomes of 9156 transplants were analysed (CIT less than 2 h in 2662, 2-4 h in 4652, and 4-8 h in 1842). After adjusting for confounders, there was no significant difference in patient survival between CIT groups. Recipients of kidneys with a CIT of 4-8 h had excellent graft outcomes, although these were slightly inferior to outcomes in those with a CIT of less than 2 h, with risk-adjusted rates of delayed graft function of 8·6 versus 4·3 per cent, and 1-year graft survival rates of 96·2 versus 97·1 per cent, respectively. CONCLUSION: The detrimental effect of prolonging CIT for up to 8 h in living donation kidney transplantation is marginal.


Subject(s)
Cold Ischemia/statistics & numerical data , Kidney Transplantation/methods , Living Donors , Organ Preservation/methods , Adult , Databases, Factual , Female , Graft Survival , Humans , Kidney Transplantation/mortality , Male , Middle Aged , Models, Statistical , Outcome Assessment, Health Care , Registries , Time Factors
7.
Transpl Infect Dis ; 17(6): 897-903, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26433132

ABSTRACT

Eumycetoma is an unusual infection in immunocompromised patients outside the tropics, caused by a variety of fungal pathogens. We describe the case of a 51-year-old renal transplant recipient who presented with a large pseudotumoral foot lesion necessitating complete surgical excision of the lesion. Cultures and molecular diagnosis confirmed Phaeoacremonium fuscum. This is the first case, to our knowledge, of fungating mycetoma caused by this fungal species in a solid organ transplant recipient.


Subject(s)
Kidney Transplantation/adverse effects , Mycetoma/diagnosis , Antifungal Agents/therapeutic use , Ascomycota/isolation & purification , Foot Diseases/microbiology , Foot Diseases/pathology , Foot Diseases/surgery , Humans , Immunocompromised Host , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Mycetoma/pathology , Mycetoma/surgery
8.
Transplant Proc ; 47(6): 1700-4, 2015.
Article in English | MEDLINE | ID: mdl-26293037

ABSTRACT

OBJECTIVE: As renal transplantation continues to evolve, there appears to be a change in both donor and recipient populations. Traditional markers of high-risk donor (e.g. donation after cardiac death [DCD]/expanded criteria donor [ECD]) and recipient (e.g. obese, highly sensitized) operations appear to be more common without any noticeable worsening of patient outcome. The present study aimed to compare outcome and define the change in donor and recipient populations for cadaveric transplants over a 10-year period at a large U.K. center. METHODS: Single-center analysis of all adult patients undergoing cadaveric renal transplantation between January 2004 and January 2014 (n = 754). Transplants were divided into 3 groups (early, middle, and late) depending on the era, with donor, recipient and outcomes compared. RESULTS: There were considerable changes in both donor and recipient factors between the 3 eras, with a greater proportion of high-risk operations performed, as reflected by significant increases in Donor Risk Index (median: 1.11-1.16, P = .022), and the proportions of ECD (22.2%-33.9%, P = .003) and DCD kidneys (10.8%-19.4% P = .011). However, 1-year graft survival was comparable between the eras, with a decrease in the average 1-year serum creatinine between the early and late cohort (median: 161 µmol/L vs 132 µmol/L, P < .001). There was no significant increase in body mass index (BMI) in either the donor or recipient population across the eras. CONCLUSION: Improvement in transplant outcome continues despite a greater proportion of transplants previously considered as high risk being performed. This is likely to reflect a considerable improvement in pre- and postoperative management. BMI remains a major continuing block to transplantation.


Subject(s)
Forecasting , Graft Survival , Kidney Transplantation/trends , Tissue Donors/supply & distribution , Adolescent , Adult , Aged , Child , Female , Humans , Male , Middle Aged , Treatment Outcome , United Kingdom , Young Adult
9.
Transplant Proc ; 47(2): 373-8, 2015 Mar.
Article in English | MEDLINE | ID: mdl-25769576

ABSTRACT

Conflicting evidence surrounds clinical outcomes in obese individuals after transplantation; nonetheless, many are denied the opportunity to receive a transplant. Allografts with complex vascular anatomy are regularly used in both deceased and living donor settings. We established the risk of transplanting kidneys with multiple renal arteries into obese recipients. A retrospective analysis of data from 1095 patients undergoing renal transplantation between January 2004 and July 2013 at a single centre was conducted. Of these, 24.2% were obese (body mass index >30 kg/m(2)), whereas 25.1% of kidneys transplanted had multiple arteries, thereby making the transplantation of kidneys of complex anatomy into obese recipients a relatively common clinical occurrence. Vessel multiplicity was associated with inferior 1-year graft survival (85.8.% vs 92.1%, P = .004). Obese patients had worse 1-graft survival compared to those of normal BMI (86.8% vs 93.8%, P = .001). The risk of vascular complications and of graft loss within a year after transplantation were greater when grafts with multiple arteries were transplanted into obese recipients as compared to their nonobese counterparts (RR 2.00, CI 95% 1.07-3.65, and RR 1.95, CI 95% 1.02-3.65). Additionally, obese patients faced significantly higher risk of graft loss if receiving a kidney with multiple arteries compared to one of normal anatomy (RR 1.97, 95% CI 1.02-3.72). Thus, obese patients receiving complex anatomy kidneys face poorer outcomes, which should be considered when allocating organs, seeking consent, and arranging for aftercare.


Subject(s)
Graft Survival , Kidney Failure, Chronic/surgery , Kidney Transplantation/adverse effects , Living Donors , Obesity/epidemiology , Renal Artery/abnormalities , Risk Assessment/methods , Adult , Body Mass Index , Female , Humans , Kidney/blood supply , Kidney/surgery , Kidney Failure, Chronic/complications , Male , Middle Aged , Obesity/etiology , Retrospective Studies , Treatment Outcome
10.
Epidemiol Infect ; 143(1): 108-19, 2015 Jan.
Article in English | MEDLINE | ID: mdl-24703238

ABSTRACT

This study developed a fast and high throughput dot-blot technique to evaluate the presence of Entamoeba in stool samples (n = 643) followed by a PCR-based method to validate and differentiate the two species E. histolytica and E. dispar. The prevalence rate of the parasite has been detected in a cross-sectional study carried out in the population of the Eastern and Northern parts of India. Of the various demographic features, prevalence was highest in the monsoon season (P = 0·017), in the <15 years age group (P = 0·015). In HIV-positive individuals, the prevalence rate was significantly high (P = 0·008) in patients with a CD4 cell count <200 as well as in patients without antiretroviral therapy (ART) (P = 0·011). Our analysis further confirmed that risk factors such as toilet facilities, living conditions, hygienic practices, drinking water source, occupation and level of education are important predictors as they were found to contribute significantly in the prevalence of the parasite.


Subject(s)
Entamoeba/isolation & purification , Entamoebiasis/diagnosis , Feces/parasitology , Molecular Diagnostic Techniques/methods , Nucleic Acid Hybridization/methods , Parasitology/methods , Adolescent , Adult , Aged , Aged, 80 and over , Child , Child, Preschool , Cross-Sectional Studies , Entamoeba/classification , Entamoeba/genetics , Entamoeba/immunology , Entamoebiasis/epidemiology , Entamoebiasis/parasitology , Female , Humans , India , Infant , Infant, Newborn , Male , Middle Aged , Prevalence , Risk Factors , Young Adult
11.
Eur J Surg Oncol ; 39(5): 450-4, 2013 May.
Article in English | MEDLINE | ID: mdl-23433860

ABSTRACT

BACKGROUND: The aim of this study was to determine whether we could identify a subset of axillary clearance patients in whom the procedure yielded negative nodes and was therefore of no therapeutic benefit. METHODS: Over a three year period 138 patients underwent axillary clearance at our unit. The axillae of all patients were assessed preoperatively with clinical examination, ultrasound (USS) and FNAC if suspicious nodes identified. Patients with clinically malignant nodes or positive FNAC underwent axillary node clearance where appropriate, whilst completion axillary node clearance was performed in those who had no preoperative evidence of metastatic axillary disease but positive sentinel node biopsy (SNB)/axillary node sample (ANS). RESULTS: Of the 138 patients, the indications for axillary clearance were positive FNAC or clinically malignant nodes in 89 and positive SNB/ANS in the remaining 49. Patients with preoperative evidence of axillary metastases had significantly more positive nodes compared to those who underwent SNB and completion ANC 4.6 vs. 3.1 p = 0.037. Of the patients with ultrasonographically normal axillae but positive SNB, 8.7% had further nodal metastases at completion ANC. This was significantly less than in those with abnormal USS (negative FNAC) and positive SNB (41.7%); p = 0.033. CONCLUSIONS: Preoperative ultrasound in conjunction with FNAC and clinical judgement identifies most patients with positive axillary nodes and such patients have more widespread disease. The additional value of completion axillary ANC in patients with ultrasonographically normal axillae but positive SNB appears small as sentinel node 'biopsy' serves to clear the axilla of metastases in most of these patients.


Subject(s)
Axilla/pathology , Breast Neoplasms/pathology , Lymphatic Metastasis/pathology , Sentinel Lymph Node Biopsy , Adult , Aged , Aged, 80 and over , Axilla/diagnostic imaging , Biopsy, Fine-Needle , Female , Humans , Lymphatic Metastasis/diagnostic imaging , Middle Aged , Ultrasonography
12.
Ann R Coll Surg Engl ; 94(6): e191-2, 2012 Sep.
Article in English | MEDLINE | ID: mdl-22943318

ABSTRACT

Intestinal malrotation is an uncommon cause of abdominal pain and normally presents during infancy. Familial cases of malrotation are extremely rare in the absence of other congenital malformations. We present the case of a 22-year-old woman with undiagnosed chronic abdominal pain and her previously well 16-year-old brother who presented within 18 months of each other with acute midgut volvulus secondary to intestinal malrotation. Clinicians should be aware of this rare but serious cause of abdominal pain.


Subject(s)
Cecal Diseases/diagnostic imaging , Duodenal Diseases/diagnostic imaging , Intestinal Volvulus/genetics , Abdominal Pain/diagnostic imaging , Abdominal Pain/genetics , Adolescent , Delayed Diagnosis , Female , Humans , Intestinal Volvulus/diagnostic imaging , Male , Siblings , Tomography, X-Ray Computed , Young Adult
14.
Colorectal Dis ; 11(5): 475-9, 2009 Jun.
Article in English | MEDLINE | ID: mdl-18616736

ABSTRACT

OBJECTIVE: Rectal cancer in young patients is uncommon. There is little information on rectal cancer in young adults in India. The aim of this study was to determine the relative incidence of rectal cancer in young patients in India and identify any differences in histological grade and pathological stage between younger and older cohorts. METHOD: All adult patients presenting at a tertiary colorectal unit with primary rectal adenocarcinoma between September 2003 and August 2007 were included. Patients were divided into two groups: 40 years and younger, and older than 40 years. Details regarding patient demographics, preoperative assessment, management and tumour grade and stage were obtained from a prospectively maintained database. RESULTS: One hundred and two of 287 patients (35.5%) were 40 or younger at presentation. Younger patients were more likely to present with less favourable histological features (52.0% vs 20.5% (P < 0.001)) and low rectal tumours (63.0% vs 50.0%) (P = 0.043), but were equally likely to undergo curative surgery compared to the older group (P = 0.629). Younger patients undergoing surgery had a higher pathological T stage (T0-2 18.9%, T3 62.3%, T4 19.7% vs 34.5%, 56.0%, 9.5%) (P = 0.027) and more advanced pathological N stage (N0 31.1%, N1 41.0%, N2 27.9% vs 53.4%, 26.7%, 17.2%) (P = 0.014). CONCLUSION: The relative number of young patients with rectal cancer in this Indian series is higher than figures reported in western populations. The reasons for this are not clear. The histopathological features of rectal tumours in young patients in this study are consistent with similar studies in Western populations.


Subject(s)
Adenocarcinoma/epidemiology , Rectal Neoplasms/epidemiology , Adenocarcinoma/pathology , Adolescent , Adult , Age Distribution , Aged , Aged, 80 and over , Female , Humans , Incidence , India/epidemiology , Male , Middle Aged , Rectal Neoplasms/pathology , Retrospective Studies , Sex Distribution , Young Adult
15.
Br J Surg ; 95(6): 721-6, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18412292

ABSTRACT

BACKGROUND: The aim of the study was to determine the value of performing peritoneal lavage cytology during laparoscopy in the management of oesophagogastric adenocarcinoma. METHODS: Laparoscopy combined with peritoneal cytology was performed in patients with potentially resectable oesophagogastric adenocarcinoma. Macroscopic peritoneal findings at laparoscopy and the presence of free peritoneal tumour cells were recorded. All patients were followed to death or the census point. Patients with overt peritoneal disease or positive cytology were offered palliative chemotherapy, subject to performance status. RESULTS: Forty-eight (18.8 per cent) of 255 patients had overt peritoneal metastases at staging laparoscopy. Fifteen (7.2 per cent) of the remaining 207 patients had positive cytology; these patients had a median (95 per cent confidence interval) survival of 13 (3.1 to 22.9) months, versus 9 (7.4 to 10.6) months for those with overt peritoneal metastases (P = 0.517). Of patients receiving chemotherapy, those without overt metastases had a slight survival advantage over patients with metastases (median 15 (10.8 to 19.2) versus 9 (7.4 to 10.7) months; P = 0.045). CONCLUSION: Positive peritoneal cytology in the absence of overt peritoneal metastases is not uncommon in oesophagogastric adenocarcinoma. It is a marker of poor prognosis even in the absence of overt peritoneal metastases.


Subject(s)
Adenocarcinoma/pathology , Esophageal Neoplasms/pathology , Peritoneal Lavage/methods , Stomach Neoplasms/pathology , Adenocarcinoma/mortality , Adult , Aged , Aged, 80 and over , Cytological Techniques/methods , Esophageal Neoplasms/mortality , Female , Humans , Laparoscopy/methods , Laparoscopy/mortality , Male , Middle Aged , Prognosis , Stomach Neoplasms/mortality , Survival Analysis
17.
Hum Reprod ; 21(11): 2868-75, 2006 Nov.
Article in English | MEDLINE | ID: mdl-16793993

ABSTRACT

BACKGROUND: Semen quality is associated with fertility status, but there is little quantitative information on risk factors that affect semen quality, especially in non-clinical populations. Advancing male age has been associated with a decline in semen quality, with the largest effect being on sperm motility. However, there is little quantitative data on the specific components of sperm motion that are affected by male age. METHODS: We performed linear regression analyses of 14 aspects of semen quality measured by computer-assisted semen analysis (CASA) in a non-clinical cohort of 90 non-smoking men, aged 22-80 years, who had no history of infertility or reproductive problems. RESULTS: We found age-associated declines in CASA-determined motility (% motile, 0.8% per year; % progressively motile, 0.9% per year; % rapidly motile, 0.4% per year, P

Subject(s)
Aging/physiology , Semen/physiology , Sperm Motility/physiology , Adult , Aged , Aged, 80 and over , Fertility , Humans , Male , Middle Aged , Sperm Count
18.
Anim Biotechnol ; 15(2): 145-57, 2004.
Article in English | MEDLINE | ID: mdl-15595700

ABSTRACT

Calpains are Ca2+-dependent intracellular cysteine proteases, including the ubiquitously expressed micro- and m-calpains. Both are heterodimers, consisting of a distinct catalytic subunit and a common regulatory subunit. We describe cloning and sequencing of the calpain small (regulatory) subunit (cpns) cDNA from rainbow trout. This represents the first fish and lower vertebrate full cDNA of cpns. The rainbow trout cpns cDNA was used to retrieve the zebra fish and Japanese flounder homologues. We present evidence that fish cpns, unlike the conventional mammalian predominant isoform, cpnsl, is lacking the glycine-rich region of domain V. Because the glycine-rich region is known to play a role in membrane targeting, this divergent cpns suggests potentially different functional and activation mechanisms of the fish calpain system. A phylogenetic tree for the cpns gene superfamily has been constructed and the evolution of cpns considered.


Subject(s)
Calpain/genetics , DNA, Complementary/analysis , Fishes/genetics , Amino Acid Sequence , Animals , Base Sequence , Calcium/metabolism , Calpain/chemistry , Evolution, Molecular , Gene Expression Regulation , Gene Library , Molecular Sequence Data , Peptide Fragments/genetics , Phylogeny , Sequence Alignment
19.
Environ Health Perspect ; 109(8): 801-8, 2001 Aug.
Article in English | MEDLINE | ID: mdl-11564615

ABSTRACT

The UROtsa cell line was isolated from a primary culture of normal human urothelium through immortalization with a construct containing the SV40 large T antigen. It proliferates in serum-containing growth medium as a cell monolayer with little evidence of uroepithelial differentiation. The working hypothesis in the present study was that this cell line could be induced to differentiate and express known features of in situ urothelium if the original serum-containing growth medium was changed to a serum-free formulation. We demonstrated that the UROtsa cells could be successfully placed into a serum-free growth medium consisting of a 1:1 mixture of Dulbeco's modified Eagle's medium and Ham's F-12 supplemented with selenium (5 ng/mL), insulin (5 microg/mL), transferrin (5 microg/mL), hydrocortisone (36 ng/mL), triiodothyronine (4 pg/mL), and epidermal growth factor (10 ng/mL). Under serum-free growth conditions, confluent UROtsa cells were shown by light microscopy to produce raised, three-dimensional structures. Routine ultrastructural examination disclosed these three-dimensional areas to consist of a stratified layer of cells that strongly resembled in situ urothelium. The cells displayed numerous desmosomal connections, complex interactions of the lateral membranes, and abundant intermediate filaments within the cytoplasm. Freeze fracture analysis demonstrated that the cells possessed tight-junction sealing strands and gap junctions. The overall morphology was most consistent with that found in the intermediate layers of in situ urothelium. The basal expression patterns of the metallothionein (MT) and heat shock proteins 27, 60, and 70 were determined in these cells, and expression was in agreement with that known to occur for in situ urothelium. The cells were also successfully tested for their ability to be stably transfected using expression vectors containing the MT-3 or MT-2A genes. The findings suggest that the UROtsa cells grown with a serum-free medium could be a valuable adjunct for studying environmental insult to the human urothelium in general and for the stress response in particular.


Subject(s)
Cell Culture Techniques/methods , Cell Line , Models, Biological , Ureter/cytology , Urothelium/cytology , Cell Division , Cell Transformation, Viral , Culture Media , Gene Expression , Heat-Shock Proteins/genetics , Humans , Kidney Tubules, Proximal , Metallothionein/biosynthesis , Protein Isoforms/biosynthesis , Protein Isoforms/genetics , RNA, Antisense/genetics , RNA, Messenger/biosynthesis , Transfection/methods
20.
Acta Psychiatr Scand ; 104(1): 72-3; discussion 74-5, 2001 Jul.
Article in English | MEDLINE | ID: mdl-11437754

ABSTRACT

OBJECTIVE: Bipolar disorder starts typically in early age and late-onset cases are rare. Late-onset cases are more likely to have comorbid medical illnesses responsible for them. This case report highlights late-onset bipolar disorder due to hyperthyroidism. METHOD: A 65-year-old patient of bipolar disorder has been described. RESULT: Physical examination and laboratory investigations detected presence of hyperthyroidism and the patient was treated with antithyroid and anxiolytics. CONCLUSION: A thorough examination and investigation are required in late-onset cases of bipolar disorder to rule out secondary causes. Definitive antimanic agents or mood stabilizers may not be required in such cases.


Subject(s)
Bipolar Disorder/etiology , Hyperthyroidism/complications , Adult , Aged , Anti-Anxiety Agents/administration & dosage , Anti-Anxiety Agents/therapeutic use , Bipolar Disorder/diagnosis , Bipolar Disorder/drug therapy , Buspirone/administration & dosage , Buspirone/therapeutic use , Humans , Hyperthyroidism/diagnosis , Male , Middle Aged , Severity of Illness Index
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