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1.
J Intellect Disabil Res ; 63(8): 969-980, 2019 08.
Article in English | MEDLINE | ID: mdl-30815933

ABSTRACT

BACKGROUND: Internationally, it has been recognised that parents need to advocate for their children with disabilities to receive services. However, many parents find advocacy difficult because of systemic and logistical barriers. As such, parents of children with disabilities may seek a special education advocate to help them understand their child's rights and secure services. Yet little research has been conducted about programmes to develop special education advocates. METHODS: In this study, we conducted a comparison study to determine the association of an advocacy programme (i.e. the Volunteer Advocacy Project) on a primary outcome (i.e. special education knowledge) and other outcomes (i.e. family-school partnership, empowerment and parent well-being). Specifically, in 2017, 34 participants, all mothers of children with disabilities, were recruited from disability organisations in the USA. Seventeen mothers participated in the intervention group (i.e. the advocacy training), while 17 mothers participated in the wait list control group. The Volunteer Advocacy Project is a 36 hr advocacy training for individuals to gain instrumental and affective knowledge to advocate for their own children with disabilities and for other families. All participants completed a pre-survey and post-survey; only intervention group participants completed a 6-month follow-up survey. RESULTS: Compared with 17 wait list control group participants, the 17 intervention group participants demonstrated improvements in special education knowledge, P = 0.002, η2  = 0.32, and self-mastery, P = 0.04, η2  = 0.15, and decreases in the quality of family-school partnerships, P = 0.002, η2  = 0.32. At the follow-up survey, intervention group participants demonstrated increases in empowerment, P = 0.04, η2  = 0.29, and special education knowledge, P = 0.02, η2  = 0.38. CONCLUSIONS: Implications for research including the need for a randomised controlled trial are discussed; also, practitioners need to evaluate advocacy training programmes regarding their effectiveness.


Subject(s)
Disabled Children/rehabilitation , Education, Nonprofessional , Education, Special , Mothers , Patient Advocacy/education , Program Evaluation , Schools , Self Efficacy , Adult , Child , Empowerment , Female , Humans , Intersectoral Collaboration , Male , Pilot Projects
2.
Transplant Proc ; 50(4): 1183-1186, 2018 May.
Article in English | MEDLINE | ID: mdl-29731090

ABSTRACT

BACKGROUND: Administrative processing by the police may affect the process involved in organ donation in the event of an accidental brain injury. The purpose of this study was to evaluate the knowledge and attitude of police toward brain-dead donors and organ donation. METHODS: This was a descriptive research study using a 41-item questionnaire. As of July 19, 2017, 11 police stations in Seoul had collected questionnaires completed by 115 police officers. Data were analyzed using SAS (version 9.4) software. RESULTS: There were statistically significant differences in the scores on knowledge about brain death/donation according to religion (P = .022). Attitude was significantly positively correlated with the knowledge about brain-death organ donation (P = .029). CONCLUSION: It is necessary to understand and cooperate with the police when processing brain death organs from accidents. Education about organ donation can enhance the information and knowledge of the police and can also help to establish a positive attitude about organ donation.


Subject(s)
Brain Death , Health Knowledge, Attitudes, Practice , Police , Tissue and Organ Procurement , Adult , Comprehension , Female , Humans , Male , Religion , Republic of Korea , Surveys and Questionnaires , Tissue Donors
3.
Oncogene ; 36(34): 4951, 2017 08 24.
Article in English | MEDLINE | ID: mdl-28604745

ABSTRACT

This corrects the article DOI: 10.1038/onc.2011.331.

4.
Clin Oncol (R Coll Radiol) ; 28(11): 695-707, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27637724

ABSTRACT

For patients with lung cancer undergoing curative intent radiotherapy, functional lung imaging can be incorporated into treatment planning to modify the dose distribution within non-target volume lung by differentiation of lung regions that are functionally defective or viable. This concept of functional image-guided lung avoidance treatment planning has been investigated with several imaging modalities, primarily single photon emission computed tomography (SPECT), but also hyperpolarised gas magnetic resonance (MR) imaging, positron emission tomography (PET) and computed tomography (CT)-based measures of lung biomechanics. Here, we review the application of each of these modalities, review practical issues of lung avoidance implementation, including image registration and the role of both ventilation and perfusion imaging, and provide guidelines for reporting of future lung avoidance planning studies.


Subject(s)
Lung Neoplasms/diagnostic imaging , Lung Neoplasms/radiotherapy , Organs at Risk/radiation effects , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Image-Guided/methods , Humans , Lung Neoplasms/pathology , Magnetic Resonance Imaging/methods , Positron-Emission Tomography/methods , Tomography, X-Ray Computed/methods
5.
ChemSusChem ; 6(10): 1973-82, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24115683

ABSTRACT

Model carbon supported Pt and Pd electrocatalysts have been prepared using a high-throughput physical vapor deposition method. For Pt, metal particle sizes are controlled between 1.5-5.5 nm over 100 electrodes of an electrochemical screening chip, allowing the oxygen reduction reaction (ORR) activity of the catalysts to be determined simultaneously. The ORR-specific current density is observed to increase with increasing particle diameter up to approximately 4 nm, at which point the activity begins to level off. The reduction in ORR activity for particles below 4 nm is accompanied by a concomitant increase in the overpotential for surface reduction. The resulting mass activity exhibits a maximum for particles with diameters of approximately 3.5 nm. These results are consistent with results published recently for high area carbon-supported Pt catalysts. For Pd particles, both the specific current density and the mass-specific activity for the ORR are observed to increase with increasing particle diameter, with no distinct optimum observed. The implications for the optimization of Pt- or Pd-based ORR catalysts for proton exchange membrane fuel cell (PEMFC) applications are discussed.


Subject(s)
Carbon/chemistry , Oxygen/chemistry , Palladium/chemistry , Particle Size , Platinum/chemistry , Electrochemistry , Oxidation-Reduction
6.
Clin Exp Dermatol ; 38(3): 244-50, 2013 Apr.
Article in English | MEDLINE | ID: mdl-23006135

ABSTRACT

BACKGROUND: Rapid skin warming and prompt correct medical treatment lead to dramatic improvement in patients with peripheral capillary-related damage, such as injuries, Raynaud disease and frostbite. AIM: To characterize a novel composite, NXCL-4950, for use in a cosmetic lotion. METHODS: The effects of NXCL-4950 on enhancing skin blood flow, skin temperature warming, and expansion of peripheral blood vessels and scalp microvessels were investigated. RESULTS: Monitoring by laser Doppler perfusion imaging and thermal imaging showed that application of NXCL-4950 to the hands increased skin blood flow and temperature relative to the control (or placebo) group. For the 20 participants with a high Raynaud Condition Score, application of NXCL-4950 to the skin resulted in a mean increase of 215.53% in microvessel diameter and mean increase of 164.96% in the speed of blood flow. When NXCL-4950 was applied to the scalp, the microvessels around the hair roots were clearly visible after 20 min. CONCLUSION: NXCL-4950 is a potential candidate for enhancing peripheral skin temperature, and might be useful in the treatment of capillary-related disorders.


Subject(s)
Complex Mixtures/therapeutic use , Peripheral Vascular Diseases/drug therapy , Plant Extracts/therapeutic use , Regional Blood Flow/drug effects , Skin Diseases/drug therapy , Skin Temperature/drug effects , Vasodilator Agents/therapeutic use , Administration, Topical , Adult , Female , Humans , Laser-Doppler Flowmetry , Male , Microvessels/drug effects , Scalp/drug effects , Skin/blood supply , Young Adult
7.
Oncogene ; 31(11): 1442-58, 2012 Mar 15.
Article in English | MEDLINE | ID: mdl-21804610

ABSTRACT

The BTB/POZ family of proteins has been implicated in multiple biological processes, including tumourigenesis, DNA damage responses and cell cycle progression and development. MIZ-1 (Myc-interacting zinc-finger protein 1) is known to activate transcription of CDKN1A. We recently found that a kidney cancer-related POK transcription factor, KR-POK, is highly expressed in kidney, brain and bone marrow cancer tissues and is a potential proto-oncoprotein. Mouse Kr-pok represses transcription of the CDKN1A by acting on the proximal promoter. The BiFC/FRET assay, co-immunoprecipitation and glutathione S-transferase-fusion protein pull-down assay indicate that MIZ-1 and Kr-pok interact via their POZ domains. Oligoucleotide pull-down assays and chromatin immunoprecipitation assays revealed that MIZ-1 binds to the proximal GC-box#3 (bp, -55 to -63) and the MIZ-1-binding elements, MRE-A (bp, -90 to -64) and MRE-B (bp, -27 to -17). Interestingly, MIZ-1 also binds to the distal p53-binding elements. Kr-pok binds to the proximal GC-box#1 (bp, -95 to -100) and #3 (bp, -55 to -63) relatively strongly. It also shows weak binding to the MREs and the distal p53-binding elements. Kr-pok competes with MIZ-1 in binding to these elements and represses transcription by inhibiting MIZ-1/p300 recruitment, which decreases the acetylation of histones H3 and H4. Our data indicate that Kr-pok stimulates cell proliferation by interfering with the function of MIZ-1 in CDKN1A gene transcription using a mechanism that is radically different from other MIZ-1-interacting proteins, such as B-cell lymphoma 6, c-Myc and Gfi-1.


Subject(s)
Cyclin-Dependent Kinase Inhibitor p21/metabolism , Kruppel-Like Transcription Factors/metabolism , Proteins/physiology , Binding, Competitive , HEK293 Cells , Humans , Intracellular Signaling Peptides and Proteins , Lymphoma, B-Cell/genetics , Promoter Regions, Genetic , Transcriptional Activation
8.
Curr Oncol ; 18(4): e163-72, 2011 Aug.
Article in English | MEDLINE | ID: mdl-21874106

ABSTRACT

For advanced and metastatic prostate cancer, androgen deprivation therapy (adt) is the mainstay of treatment. Awareness of the potential bone-health complications consequent to adt use is increasing. Many studies have shown that prolonged adt leads to significant bone loss and increased fracture risk that negatively affect quality of life. Clinical practice guidelines for preserving bone health in men with prostate cancer on adt vary across Canada. This paper reviews recent studies on bone health in men with prostate cancer receiving adt and the current evidence regarding bone-health monitoring and management in reference to Canadian provincial guidelines. Based on this narrative review, we provide general bone-health management recommendations for men with prostate cancer receiving adt.

9.
Singapore Med J ; 52(5): 361-4, 2011 May.
Article in English | MEDLINE | ID: mdl-21633771

ABSTRACT

INTRODUCTION: The incidence of Clostridium (C.) difficile infection (CDI) was on the rise from 2001 to 2006 in Singapore. Recent unpublished data suggests that its incidence had remained stable or decreased in most local public hospitals between 2006 and 2010. It is, however, not known if the polymerase chain reaction (PCR) ribotype 027 strains have been circulating, although reports suggest that this strain is emerging in Asia, with the first cases reported from Japan in 2007, as well as in Hong Kong and Australia in 2009. We initiated a culture-based surveillance to detect this epidemic strain in Singapore. METHODS: From September 2008 to December 2009, all non-duplicate toxin-positive stool samples from the three largest public hospitals in Singapore were collected for culture and further analysis. RESULTS: Out of the 366 samples collected, 272 viable isolates were cultured. Of these, 240 tested toxin-positive and ten tested positive for the binary toxin gene; 35 different PCR ribotypes were found. Three isolates that tested positive for binary toxin contained the same PCR ribotyping pattern as the C. difficile 027 control strain. All three had the 18-bp deletion and single nucleotide tcdC deletion at position 117. Susceptibility testing was performed, demonstrating susceptibility to erythromycin and moxifloxacin. CONCLUSION: We report the first three isolates of C. difficile 027 from Singapore. However, their susceptibility patterns are more consistent with the historical 027 strains. Rising CDI incidence may not be associated with the emergence of the epidemic 027 strain at this time.


Subject(s)
Clostridioides difficile/genetics , Clostridium Infections/genetics , Polymerase Chain Reaction/methods , Bacterial Typing Techniques , Clostridium Infections/epidemiology , Cross Infection , Drug Resistance, Bacterial/genetics , Epidemics , Hospitals, Public , Humans , Microbial Sensitivity Tests , Prospective Studies , Ribotyping , Singapore
10.
Clin Oncol (R Coll Radiol) ; 23(2): 73-8, 2011 Mar.
Article in English | MEDLINE | ID: mdl-21168314

ABSTRACT

Collagen vascular diseases (CVD) are a group of chronic, autoimmune conditions that can affect multiple organ systems. The mainstay of treatment involves the use of immunosuppressants. CVDs and immunosuppression increase the risk of these patients developing malignancy. The mechanisms through which these patients develop CVDs show similarities to those for radiotherapy late effects, especially fibrosis (via transforming growth factor ß). Radiotherapy may in fact cause an active state to develop from a quiescent state of CVD, or exacerbate a pre-existing CVD. CVDs are said to be associated with increased normal tissue toxicity after radiotherapy. Here we present a case report of a patient with a long history of systemic lupus erythematosus and oropharyngeal carcinoma, treated with synchronous chemoradiotherapy. We also review published studies and formulate some guidance on the radiotherapy management of these patients.


Subject(s)
Carcinoma/drug therapy , Carcinoma/radiotherapy , Lupus Erythematosus, Systemic/complications , Oropharyngeal Neoplasms/drug therapy , Oropharyngeal Neoplasms/radiotherapy , Radiation Injuries/etiology , Collagen Diseases/complications , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Humans , Male , Middle Aged , Practice Guidelines as Topic , Radiotherapy/adverse effects , Vascular Diseases/complications
11.
Neuroscience ; 173: 37-56, 2011 Jan 26.
Article in English | MEDLINE | ID: mdl-21093546

ABSTRACT

Humans and mice with loss-of-function mutations of the genes encoding kisspeptins (Kiss1) or kisspeptin receptor (Kiss1r) are infertile due to hypogonadotropic hypogonadism. Within the hypothalamus, Kiss1 mRNA is expressed in the anteroventral periventricular nucleus (AVPV) and the arcuate nucleus (Arc). In order to better study the different populations of kisspeptin cells we generated Kiss1-Cre transgenic mice. We obtained one line with Cre activity specifically within Kiss1 neurons (line J2-4), as assessed by generating mice with Cre-dependent expression of green fluorescent protein or ß-galactosidase. Also, we demonstrated Kiss1 expression in the cerebral cortex and confirmed previous data showing Kiss1 mRNA in the medial nucleus of amygdala and anterodorsal preoptic nucleus. Kiss1 neurons were more concentrated towards the caudal levels of the Arc and higher leptin-responsivity was observed in the most caudal population of Arc Kiss1 neurons. No evidence for direct action of leptin in AVPV Kiss1 neurons was observed. Melanocortin fibers innervated subsets of Kiss1 neurons of the preoptic area and Arc, and both populations expressed melanocortin receptors type 4 (MC4R). Specifically in the preoptic area, 18-28% of Kiss1 neurons expressed MC4R. In the Arc, 90% of Kiss1 neurons were glutamatergic, 50% of which also were GABAergic. In the AVPV, 20% of Kiss1 neurons were glutamatergic whereas 75% were GABAergic. The differences observed between the Kiss1 neurons in the preoptic area and the Arc likely represent neuronal evidence for their differential roles in metabolism and reproduction.


Subject(s)
Brain/metabolism , Neurons/metabolism , Proteins/metabolism , Animals , Brain/cytology , Cell Separation , Disease Models, Animal , Female , Flow Cytometry , Immunohistochemistry , In Situ Hybridization , Kisspeptins , Male , Mice , Mice, Inbred C57BL , Mice, Transgenic , Neurons/cytology , Reverse Transcriptase Polymerase Chain Reaction
12.
Med J Malaysia ; 65(3): 221-3, 2010 Sep.
Article in English | MEDLINE | ID: mdl-21939173

ABSTRACT

We report a case of a 21-year-old university student with underlying lupus nephritis who presented with recurrent symptoms of fever, haemoptysis, and pleuritic chest pain. CT pulmonary angiogram confirmed pulmonary embolism in the right subsegmental pulmonary arteries. One week later, she developed left renal vein and left common iliac vein thromboses, with new emboli in the left subsegmental pulmonary arteries. We hereforth discuss the diagnostic issues of a patient with systemic lupus erythematosus (SLE) on corticosteroids therapy, and also treatment of the antiphospholipid syndrome.


Subject(s)
Antiphospholipid Syndrome/complications , Antiphospholipid Syndrome/diagnosis , Lupus Erythematosus, Systemic/complications , Pulmonary Embolism/complications , Venous Thrombosis/complications , Adult , Anticoagulants/therapeutic use , Antiphospholipid Syndrome/drug therapy , Female , Humans , Pulmonary Embolism/diagnostic imaging , Radiography , Venous Thrombosis/diagnostic imaging , Young Adult
13.
Med J Malaysia ; 65(1): 63-5, 2010 Mar.
Article in English | MEDLINE | ID: mdl-21265252

ABSTRACT

We report seven cases of naturally acquired human Plasmodium knowlesi infections which were admitted to our centre from July 2007 till June 2008. Diagnosis was confirmed by nested PCR. Cases of P. knowlesi infections, dubbed the fifth type of human malaria, have been reported in East Malaysia (Sabah and Sarawak) as well as in the state of Pahang in Peninsula Malaysia. These seven patients appear to be the first few reported cases of P. knowlesi infection in the Klang valley, Peninsula Malaysia. We then discuss the characteristics of human P. knowlesi infections, which include its natural hosts, responsible vectors, clinical presentation, and the treatment of such infections.


Subject(s)
Malaria/diagnosis , Plasmodium knowlesi , Adolescent , Adult , Female , Humans , Malaria/drug therapy , Malaysia , Male , Middle Aged
14.
Med J Malaysia ; 65(1): 72-4, 2010 Mar.
Article in English | MEDLINE | ID: mdl-21265256

ABSTRACT

We report a case of a 61 year-old man who presented with refractory non-insulin mediated hypoglycaemia. A chest radiograph showed a right lung opacity, which was confirmed as a large intra-thoracic mass by computed tomography (CT) of the thorax. CT-guided biopsy with histological examination revealed features of a solitary fibrous tumour of low malignant potential. We discuss the association of solitary fibrous tumour of the pleura (SFTP) with hypoglycaemia, and the management of such rare tumours.


Subject(s)
Hypoglycemia/etiology , Pleural Neoplasms/complications , Solitary Fibrous Tumors/complications , Humans , Male , Middle Aged , Pleural Neoplasms/pathology , Pleural Neoplasms/therapy , Solitary Fibrous Tumors/pathology , Solitary Fibrous Tumors/therapy , Tomography, X-Ray Computed
15.
Oncogene ; 28(35): 3145-56, 2009 Sep 03.
Article in English | MEDLINE | ID: mdl-19561639

ABSTRACT

Suppressors of cytokine signaling (SOCS) are negative regulators of cytokine-induced signal transduction, which play multiple roles in cell growth, differentiation and apoptosis. In this study, the regulatory role of SOCS in oxidative stress-induced apoptosis was investigated. In Jurkat T cells and mouse splenocytes, we have found that SOCS1 is induced in response to tumor necrosis factor-alpha or H(2)O(2), concomitant with the activation of Jaks which act as important mediators of reactive oxygen species (ROS)-induced apoptosis upstream of p38 mitogen-activated protein kinase. Using SOCS1 overexpressing or knockdown Jurkat T-cell systems we clearly demonstrate that, SOCS1 inhibits the ROS-mediated apoptosis. The antiapoptotic action of SOCS1 was exerted not only by suppressing Jaks, but also by sustaining protein tyrosine phosphatase (PTP) activities. Notably, SOCS1-transduced cells displayed increase in thioredoxin levels and decrease in ROS generation induced by oxidative stress. In addition, the Jak-inhibiting and PTP-sustaining effect of SOCS1 was significantly reduced on thioredoxin ablation. Moreover, coimmunoprecipitation data revealed molecular interaction of SHP1 or CD45 with thioredoxin, which was promoted in SOCS1-transfected cells. Together, our data strongly suggest that both the protection of PTPs by thioredoxin from ROS attack and the attenuation of Jaks account for the antiapoptotic function of SOCS1 in immune cells under oxidative stress.


Subject(s)
Apoptosis/genetics , Protein Methyltransferases/metabolism , Protein Tyrosine Phosphatases/metabolism , Suppressor of Cytokine Signaling Proteins/metabolism , Thioredoxins/metabolism , Apoptosis/drug effects , Cell Line , Dexamethasone/pharmacology , Humans , Hydrogen Peroxide/pharmacology , Interferon-gamma/pharmacology , Jurkat Cells , Oxidative Stress/genetics , Protein-Arginine N-Methyltransferases , RNA, Messenger/metabolism , RNA, Small Interfering/metabolism , Reactive Oxygen Species/metabolism , Suppressor of Cytokine Signaling 1 Protein , Suppressor of Cytokine Signaling Proteins/biosynthesis , T-Lymphocytes/metabolism , Transfection , Tumor Necrosis Factor-alpha/pharmacology , Up-Regulation
16.
Diabetologia ; 52(6): 1092-101, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19343319

ABSTRACT

AIMS/HYPOTHESIS: The destruction of pancreatic beta cells leading to type 1 diabetes in humans is thought to occur mainly through apoptosis and necrosis induced by activated macrophages and T cells, and in which secreted cytokines play a significant role. The transcription factor nuclear factor kappa-B (NF-kappaB) plays an important role in mediating the apoptotic action of cytokines in beta cells. We therefore sought to determine the changes in expression of genes modulated by NF-kappaB in human islets exposed to a combination of IL1beta, TNF-alpha and IFN-gamma. METHODS: Microarray and gene set enrichment analysis were performed to investigate the global response of gene expression and pathways modulated in cultured human islets exposed to cytokines. Validation of a panel of NF-kappaB-regulated genes was performed by quantitative RT-PCR. The mechanism of induction of BIRC3 by cytokines was examined by transient transfection of BIRC3 promoter constructs linked to a luciferase gene in MIN6 cells, a mouse beta cell line. RESULTS: Enrichment of several metabolic and signalling pathways was observed in cytokine-treated human islets. In addition to the upregulation of known pro-apoptotic genes, a number of anti-apoptotic genes including BIRC3, BCL2A1, TNFAIP3, CFLAR and TRAF1 were induced by cytokines through NF-kappaB. Significant synergy between the cytokines was observed in NF-kappaB-mediated induction of the promoter of BIRC3 in MIN6 cells. CONCLUSIONS/INTERPRETATION: These findings suggest that, via NF-kappaB activation, cytokines induce a concurrent anti-apoptotic pathway that may be critical for preserving islet integrity and viability during the progression of insulitis in type 1 diabetes.


Subject(s)
Cytokines/pharmacology , Insulin-Secreting Cells/drug effects , Insulin-Secreting Cells/metabolism , Islets of Langerhans/drug effects , Islets of Langerhans/metabolism , NF-kappa B/metabolism , Animals , Baculoviral IAP Repeat-Containing 3 Protein , CASP8 and FADD-Like Apoptosis Regulating Protein/genetics , Cell Line , Cells, Cultured , DNA-Binding Proteins/genetics , Humans , Inhibitor of Apoptosis Proteins/genetics , Interferon-gamma/pharmacology , Interleukin-1beta/pharmacology , Mice , Minor Histocompatibility Antigens , Oligonucleotide Array Sequence Analysis , Proto-Oncogene Proteins c-bcl-2/genetics , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/drug effects , TNF Receptor-Associated Factor 1/genetics , Tumor Necrosis Factor-alpha/pharmacology , Ubiquitin-Protein Ligases
17.
Med J Malaysia ; 64(4): 330-2, 2009 Dec.
Article in English | MEDLINE | ID: mdl-20954563

ABSTRACT

We report a case of a 52 year-old dentist who had stent implantation for a left subclavian artery stenosis. However, this was later complicated by a stent fracture within one week of stent placement. A chest radiograph showed two pieces of the fractured stent, which was confirmed by computed tomographic angiogram (CTA) of the affected artery. We then discuss the occurrence of stent fractures, which are not uncommon but serious complications of endovascular therapy.


Subject(s)
Stents/adverse effects , Subclavian Steal Syndrome/therapy , Female , Humans , Middle Aged , Subclavian Artery/diagnostic imaging , Subclavian Steal Syndrome/diagnostic imaging , Tomography, X-Ray Computed
19.
Immunogenetics ; 57(12): 917-25, 2006 Jan.
Article in English | MEDLINE | ID: mdl-16402215

ABSTRACT

We have used a bioinformatics approach to evaluate the completeness and functionality of the reported human immunoglobulin heavy-chain IGHD gene repertoire. Using the hidden Markov-model-based iHMMune-align program, 1,080 relatively unmutated heavy-chain sequences were aligned against the reported repertoire. These alignments were compared with alignments to 1,639 more highly mutated sequences. Comparisons of the frequencies of gene utilization in the two databases, and analysis of features of aligned IGHD gene segments, including their length, the frequency with which they appear to mutate, and the frequency with which specific mutations were seen, were used to determine the reliability of alignments to the less commonly seen IGHD genes. Analysis demonstrates that IGHD4-23 and IGHD5-24, which have been reported to be open reading frames of uncertain functionality, are represented in the expressed gene repertoire; however, the functionality of IGHD6-25 must be questioned. Sequence similarities make the unequivocal identification of members of the IGHD1 gene family problematic, although all genes except IGHD1-14*01 appear to be functional. On the other hand, reported allelic variants of IGHD2-2 and of the IGHD3 gene family appear to be nonfunctional, very rare, or nonexistent. Analysis also suggests that the reported repertoire is relatively complete, although one new putative polymorphism (IGHD3-10*p03) was identified. This study therefore confirms a surprising lack of diversity in the available IGHD gene repertoire, and restriction of the germline sequence databases to the functional set described here will substantially improve the accuracy of IGHD gene alignments and therefore the accuracy of analysis of the V-D-J junction.


Subject(s)
Genes, Immunoglobulin , Immunoglobulin Heavy Chains/genetics , Immunoglobulin delta-Chains/genetics , Alleles , Computational Biology , Databases, Nucleic Acid , Gene Expression , Gene Frequency , Genetic Variation , Humans , Markov Chains , Point Mutation , Sequence Alignment
20.
Appl Microbiol Biotechnol ; 69(4): 456-62, 2005 Dec.
Article in English | MEDLINE | ID: mdl-15856223

ABSTRACT

A modeling study was conducted on growth kinetics of three different strains of Pseudomonas spp. (Pseudomonas aeruginosa, Pseudomonas fluorescens, Pseudomonas putida) during benzene degradation to determine optimum substrate concentrations for most efficient biodegradation. Batch tests were performed for eight different initial substrate concentrations to observe cell growth and associated substrate degradation using benzene-adapted cells. Kinetic parameters of both inhibitory (Haldane-Andrews, Aiba-Edwards) and noninhibitory (Monod) models were fitted to the relationship between specific growth rate and substrate concentration obtained from the growth curves. Results showed that half-saturation constant of P. fluorescens was the highest among the three strains, indicating that this strain could grow well at high concentration, while P. putida could grow best at low concentration. The inhibition constant of P. aeruginosa was the highest, implying that it could tolerate high benzene concentration and therefore could grow at a wider concentration range. Estimated specific growth rate of P. putida was lower, but half-saturation constant was higher than those from literature study due to high substrate concentration range used in this study. These two kinetic parameters resulted in substantial difference between Monod- and Haldane-type models, indicating that distinction should be made in applying those models.


Subject(s)
Benzene/metabolism , Models, Biological , Pseudomonas/growth & development , Biodegradation, Environmental , Biotechnology/methods , Culture Media , Kinetics , Pseudomonas/classification , Pseudomonas/metabolism , Substrate Specificity
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