Author Report for: Johnson TNo contact information in database for Johnson T
Thapa S, Li H, J OH, Bhatti S, Chen FC, Nasr KA, Johnson T, Zhou S Ref: Mol Biotechnol, 61:579, 2019 : PubMed ESTHER: Thapa_2019_Mol.Biotechnol_61_579 PubMedSearch: Thapa 2019 Mol.Biotechnol 61 579 PubMedID: 31168761 Abstract Microbes are ubiquitously distributed in nature and are a critical part of the holobiont fitness. They are perceived as the most potential biochemical reservoir of inordinately diverse and multi-functional enzymes. The robust nature of the microbial enzymes with thermostability, pH stability and multi-functionality make them potential candidates for the efficient biotechnological processes under diverse physio-chemical conditions. The need for sustainable solutions to various environmental challenges has further surged the demand for industrial enzymes. Fueled by the recent advent of recombinant DNA technology, genetic engineering, and high-throughput sequencing and omics techniques, numerous microbial enzymes have been developed and further exploited for various industrial and therapeutic applications. Most of the hydrolytic enzymes (protease being the dominant hydrolytic enzyme) have broad range of industrial uses such as food and feed processing, polymer synthesis, production of pharmaceuticals, manufactures of detergents, paper and textiles, and bio-fuel refinery. In this review article, after a short overview of microbial enzymes, an approach has been made to highlight and discuss their potential relevance in biotechnological applications and industrial bio-processes, significant biochemical characteristics of the microbial enzymes, and various tools that are revitalizing the novel enzymes discovery. Title: A phenome-wide association study of a lipoprotein-associated phospholipase A2 loss-of-function variant in 90 000 Chinese adults Millwood IY, Bennett DA, Walters RG, Clarke R, Waterworth D, Johnson T, Chen Y, Yang L, Guo Y and Chen Z <10 more author(s)> Millwood IY, Bennett DA, Walters RG, Clarke R, Waterworth D, Johnson T, Chen Y, Yang L, Guo Y, Bian Z, Hacker A, Yeo A, Parish S, Hill MR, Chissoe S, Peto R, Cardon L, Collins R, Li L, Chen Z (- 10) Ref: Int J Epidemiol, 45:1588, 2016 : PubMed ESTHER: Millwood_2016_Int.J.Epidemiol_45_1588 PubMedSearch: Millwood 2016 Int.J.Epidemiol 45 1588 PubMedID: 27301456 Gene_locus related to this paper: human-PLA2G7 Abstract BACKGROUND: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) has been implicated in development of atherosclerosis; however, recent randomized trials of Lp-PLA(2) inhibition reported no beneficial effects on vascular diseases. In East Asians, a loss-of-function variant in the PLA2G7 gene can be used to assess the effects of genetically determined lower Lp-PLA(2) METHODS: PLA2G7 V279F (rs76863441) was genotyped in 91 428 individuals randomly selected from the China Kadoorie Biobank of 0.5 M participants recruited in 2004-08 from 10 regions of China, with 7 years' follow-up. Linear regression was used to assess effects of V279F on baseline traits. Logistic regression was conducted for a range of vascular and non-vascular diseases, including 41 ICD-10 coded disease categories. RESULTS: PLA2G7 V279F frequency was 5% overall (range 3-7% by region), and 9691 (11%) participants had at least one loss-of-function variant. V279F was not associated with baseline blood pressure, adiposity, blood glucose or lung function. V279F was not associated with major vascular events [7141 events; odds ratio (OR) = 0.98 per F variant, 95% confidence interval (CI) 0.90-1.06] or other vascular outcomes, including major coronary events (922 events; 0.96, 0.79-1.18) and stroke (5967 events; 1.00, 0.92-1.09). Individuals with V279F had lower risks of diabetes (7031 events; 0.91, 0.84-0.98) and asthma (182 events; 0.53, 0.28-0.98), but there was no association after adjustment for multiple testing. CONCLUSIONS: Lifelong lower Lp-PLA(2) activity was not associated with major risks of vascular or non-vascular diseases in Chinese adults. Using functional genetic variants in large-scale prospective studies with linkage to a range of health outcomes is a valuable approach to inform drug development and repositioning. Title: Donepezil and memantine for moderate-to-severe Alzheimer's disease Howard R, McShane R, Lindesay J, Ritchie C, Baldwin A, Barber R, Burns A, Dening T, Findlay D and Phillips P <22 more author(s)> Howard R, McShane R, Lindesay J, Ritchie C, Baldwin A, Barber R, Burns A, Dening T, Findlay D, Holmes C, Hughes A, Jacoby R, Jones R, McKeith I, Macharouthu A, O'Brien J, Passmore P, Sheehan B, Juszczak E, Katona C, Hills R, Knapp M, Ballard C, Brown R, Banerjee S, Onions C, Griffin M, Adams J, Gray R, Johnson T, Bentham P, Phillips P (- 22) Ref: N Engl J Med, 366:893, 2012 : PubMed ESTHER: Howard_2012_N.Engl.J.Med_366_893 PubMedSearch: Howard 2012 N.Engl.J.Med 366 893 PubMedID: 22397651 Abstract BACKGROUND: Clinical trials have shown the benefits of cholinesterase inhibitors for the treatment of mild-to-moderate Alzheimer's disease. It is not known whether treatment benefits continue after the progression to moderate-to-severe disease. METHODS: We assigned 295 community-dwelling patients who had been treated with donepezil for at least 3 months and who had moderate or severe Alzheimer's disease (a score of 5 to 13 on the Standardized Mini-Mental State Examination [SMMSE, on which scores range from 0 to 30, with higher scores indicating better cognitive function]) to continue donepezil, discontinue donepezil, discontinue donepezil and start memantine, or continue donepezil and start memantine. Patients received the study treatment for 52 weeks. The coprimary outcomes were scores on the SMMSE and on the Bristol Activities of Daily Living Scale (BADLS, on which scores range from 0 to 60, with higher scores indicating greater impairment). The minimum clinically important differences were 1.4 points on the SMMSE and 3.5 points on the BADLS. RESULTS: Patients assigned to continue donepezil, as compared with those assigned to discontinue donepezil, had a score on the SMMSE that was higher by an average of 1.9 points (95% confidence interval [CI], 1.3 to 2.5) and a score on the BADLS that was lower (indicating less impairment) by 3.0 points (95% CI, 1.8 to 4.3) (P<0.001 for both comparisons). Patients assigned to receive memantine, as compared with those assigned to receive memantine placebo, had a score on the SMMSE that was an average of 1.2 points higher (95% CI, 0.6 to 1.8; P<0.001) and a score on the BADLS that was 1.5 points lower (95% CI, 0.3 to 2.8; P=0.02). The efficacy of donepezil and of memantine did not differ significantly in the presence or absence of the other. There were no significant benefits of the combination of donepezil and memantine over donepezil alone. CONCLUSIONS: In patients with moderate or severe Alzheimer's disease, continued treatment with donepezil was associated with cognitive benefits that exceeded the minimum clinically important difference and with significant functional benefits over the course of 12 months. (Funded by the U.K. Medical Research Council and the U.K. Alzheimer's Society; Current Controlled Trials number, ISRCTN49545035.). Title: Characterization and differential gene expression between two phenotypic phase variants in Salmonella enterica serovar Typhimurium Patterson SK, Borewicz K, Johnson T, Xu W, Isaacson RE Ref: PLoS ONE, 7:e43592, 2012 : PubMed ESTHER: Patterson_2012_PLoS.One_7_e43592 PubMedSearch: Patterson 2012 PLoS.One 7 e43592 PubMedID: 22937065 Abstract Salmonella enterica serovar Typhimurium strain 798 has previously been shown to undergo phenotypic phase variation. One of the phenotypes expresses virulence traits such as adhesion, while the other phenotype does not. Phenotypic phase variation appears to correlate with the ability of this strain to cause persistent, asymptomatic infections of swine. A new method to detect cells in either phenotypic phase was developed using Evans Blue-Uranine agar plates. Using this new assay, rates of phenotypic phase variation were obtained. The rate of phase variation from non-adhesive to adhesive phenotype was approximately 10(-4) per cell per generation while phase variation from the adhesive to the non-adhesive phenotype was approximately 10(-6) per cell per generation. Two highly virulent S. Typhimurium strains, SL1344 and ATCC 14028, were also shown to undergo phase variation. However, while the rate from adhesive to non-adhesive phenotype was approximately the same as for strain 798, the non-adhesive to adhesive phenotype shift was 37-fold higher. Differential gene expression was measured using RNA-Seq. Eighty-three genes were more highly expressed by 798 cells in the adhesive phenotype compared to the non-adhesive cells. Most of the up-regulated genes were in virulence genes and in particular all genes in the Salmonella pathogenicity island 1 were up-regulated. When compared to the virulent strain SL1344, expression of the virulence genes was approximately equal to those up-regulated in the adhesive phenotype of strain 798. A comparison of invasive ability demonstrated that strain SL1344 was the most invasive followed by the adhesive phenotype of strain 798, then the non-adhesive phenotype of strain 798. The least invasive strain was ATCC 14028. The genome of strain 798 was sequenced and compared to SL1344. Both strains had very similar genome sequences and gene deletions could not readily explain differences in the rates of phase variation from non-adhesive to the adhesive phenotype. Title: Brief psychosocial therapy for the treatment of agitation in Alzheimer disease (the CALM-AD trial) Ballard C, Brown R, Fossey J, Douglas S, Bradley P, Hancock J, James IA, Juszczak E, Bentham P and Howard R <7 more author(s)> Ballard C, Brown R, Fossey J, Douglas S, Bradley P, Hancock J, James IA, Juszczak E, Bentham P, Burns A, Lindesay J, Jacoby R, O'Brien J, Bullock R, Johnson T, Holmes C, Howard R (- 7) Ref: American Journal of Geriatry & Psychiatry, 17:726, 2009 : PubMed ESTHER: Ballard_2009_Am.J.Geriatr.Psychiatry_17_726 PubMedSearch: Ballard 2009 Am.J.Geriatr.Psychiatry 17 726 PubMedID: 19700946 Abstract BACKGROUND: Good practice guidelines state that a psychological intervention should usually precede pharmacotherapy, but there are no data evaluating the feasibility of psychological interventions used in this way. METHODS: At the first stage of a randomized blinded placebo-controlled trial, 318 patients with Alzheimer disease (AD) with clinically significant agitated behavior were treated in an open design with a psychological intervention (brief psychosocial therapy [BPST]) for 4 weeks, preceding randomization to pharmacotherapy. The therapy involved social interaction, personalized music, or removal of environmental triggers. RESULTS: Overall, 318 patients with AD completed BPST with an improvement of 5.6 points on the total Cohen-Mansfield Agitation Inventory (CMAI; mean [SD], 63.3 [16.0] to 57.7 [18.4], t = 4.8, df = 317, p < 0.0001). Therapy worksheets were completed in six of the eight centers, with the key elements of the intervention delivered according to the manual for >95% of patients. More detailed evaluation of outcome was completed for the 198 patients with AD from these centers, who experienced a mean improvement of 6.6 points on the total CMAI (mean [SD], 62.2 [14.3] to 55.6 [15.8], t = 6.5, df = 197, p < 0.0001). Overall, 43% of participants achieved a 30% improvement in their level of agitation. CONCLUSION: The specific attributable benefits of BPST cannot be determined from an open trial. However, the BPST therapy was feasible and was successfully delivered according to an operationalized manual. The encouraging outcome indicates the need for a randomized controlled trial of BPST. Title: DOMINO-AD protocol: donepezil and memantine in moderate to severe Alzheimer's disease - a multicentre RCT Jones R, Sheehan B, Phillips P, Juszczak E, Adams J, Baldwin A, Ballard C, Banerjee S, Barber B and Howard R <21 more author(s)> Jones R, Sheehan B, Phillips P, Juszczak E, Adams J, Baldwin A, Ballard C, Banerjee S, Barber B, Bentham P, Brown R, Burns A, Dening T, Findlay D, Gray R, Griffin M, Holmes C, Hughes A, Jacoby R, Johnson T, Knapp M, Lindesay J, McKeith I, McShane R, Macharouthu A, O'Brien J, Onions C, Passmore P, Raftery J, Ritchie C, Howard R (- 21) Ref: Trials, 10:57, 2009 : PubMed ESTHER: Jones_2009_Trials_10_57 PubMedSearch: Jones 2009 Trials 10 57 PubMedID: 19630974 Abstract BACKGROUND: Alzheimer's disease (AD) is the commonest cause of dementia. Cholinesterase inhibitors, such as donepezil, are the drug class with the best evidence of efficacy, licensed for mild to moderate AD, while the glutamate antagonist memantine has been widely prescribed, often in the later stages of AD. Memantine is licensed for moderate to severe dementia in AD but is not recommended by the England and Wales National Institute for Health and Clinical Excellence. However, there is little evidence to guide clinicians as to what to prescribe as AD advances; in particular, what to do as the condition progresses from moderate to severe. Options include continuing cholinesterase inhibitors irrespective of decline, adding memantine to cholinesterase inhibitors, or prescribing memantine instead of cholinesterase inhibitors. The aim of this trial is to establish the most effective drug option for people with AD who are progressing from moderate to severe dementia despite treatment with donepezil. METHOD: DOMINO-AD is a pragmatic, 15 centre, double-blind, randomized, placebo controlled trial. Patients with AD, currently living at home, receiving donepezil 10 mg daily, and with Standardized Mini-Mental State Examination (SMMSE) scores between 5 and 13 are being recruited. Each is randomized to one of four treatment options: continuation of donepezil with memantine placebo added; switch to memantine with donepezil placebo added; donepezil and memantine together; or donepezil placebo with memantine placebo. 800 participants are being recruited and treatment continues for one year. Primary outcome measures are cognition (SMMSE) and activities of daily living (Bristol Activities of Daily Living Scale). Secondary outcomes are non-cognitive dementia symptoms (Neuropsychiatric Inventory), health related quality of life (EQ-5D and DEMQOL-proxy), carer burden (General Health Questionnaire-12), cost effectiveness (using Client Service Receipt Inventory) and institutionalization. These outcomes are assessed at baseline, 6, 18, 30 and 52 weeks. All participants will be subsequently followed for 3 years by telephone interview to record institutionalization. DISCUSSION: There is considerable debate about the clinical and cost effectiveness of anti-dementia drugs. DOMINO-AD seeks to provide clear evidence on the best treatment strategies for those managing patients at a particularly important clinical transition point. TRIAL REGISTRATION: Current controlled trials ISRCTN49545035. Title: Donepezil for the treatment of agitation in Alzheimer's disease Howard RJ, Juszczak E, Ballard CG, Bentham P, Brown RG, Bullock R, Burns AS, Holmes C, Jacoby R and Rodger M <8 more author(s)> Howard RJ, Juszczak E, Ballard CG, Bentham P, Brown RG, Bullock R, Burns AS, Holmes C, Jacoby R, Johnson T, Knapp M, Lindesay J, O'Brien JT, Wilcock G, Katona C, Jones RW, DeCesare J, Rodger M (- 8) Ref: N Engl J Med, 357:1382, 2007 : PubMed ESTHER: Howard_2007_N.Engl.J.Med_357_1382 PubMedSearch: Howard 2007 N.Engl.J.Med 357 1382 PubMedID: 17914039 Abstract BACKGROUND: Agitation is a common and distressing symptom in patients with Alzheimer's disease. Cholinesterase inhibitors improve cognitive outcomes in such patients, but the benefits of these drugs for behavioral disturbances are unclear. | |||||||
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