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Article ; Online: Lung Cancer Surgery in the Early Phase After Acute COVID-19 Pneumonitis.

Robinson, Dean P / Smith, Alexander E / Okiror, Lawrence

2021 Volume 113, Issue 4, Page(s) e243–e245

Abstract: A 65-year-old woman was diagnosed with early-stage lung cancer in 2020 and scheduled for robotic assisted-left upper lobectomy. Unfortunately, the patient contracted symptomatic COVID-19, resulting in postponement of lung resection. She was admitted for ... ...

Abstract	A 65-year-old woman was diagnosed with early-stage lung cancer in 2020 and scheduled for robotic assisted-left upper lobectomy. Unfortunately, the patient contracted symptomatic COVID-19, resulting in postponement of lung resection. She was admitted for surgery 6 weeks after the acute infection. A preoperative computed tomographic scan showed widespread interstitial pneumonitis. However, the operation went ahead given concerns over tumor progression, albeit with a lesser resection to preserve lung tissue because the patient was slightly hypoxic. Her postoperative recovery was uneventful, and she was discharged 5 days later. Final histology confirmed a fully resected stage T1c N0 M0 adenocarcinoma of the lung.
MeSH term(s)	Adenocarcinoma/complications ; Adenocarcinoma/diagnosis ; Adenocarcinoma/surgery ; Aged ; COVID-19 ; Female ; Humans ; Lung Neoplasms/pathology ; Pneumonectomy/methods ; Pneumonia/surgery
Language	English
Publishing date	2021-07-01
Publishing country	Netherlands
Document type	Case Reports
ZDB-ID	211007-6
ISSN	1552-6259 ; 0003-4975
ISSN (online)	1552-6259
ISSN	0003-4975
DOI	10.1016/j.athoracsur.2021.06.016
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Article ; Online: Synchronous Parathyroidectomy and Extended Thymectomy in Multiple Endocrine Neoplasia Type 1.

Robinson, Dean P / Smith, Alexander E P / Bille, Andrea / Simo, Ricard

The Annals of thoracic surgery

2021 Volume 114, Issue 2, Page(s) e85–e88

Abstract: A 49-year-old man presented with symptoms of hypercalcemia that had been present for 3 months. An initial chest x-ray showed a large anterior mediastinal mass. Subsequent computed tomography also demonstrated a calcified lesion in the uncinate process of ...

Abstract	A 49-year-old man presented with symptoms of hypercalcemia that had been present for 3 months. An initial chest x-ray showed a large anterior mediastinal mass. Subsequent computed tomography also demonstrated a calcified lesion in the uncinate process of the pancreas, and a neck ultrasound showed parathyroid lesions. The combination of symptoms and tumors raised the possibility of multiple endocrine neoplasia type 1 as the diagnosis. The lesions were later biopsy-proven to be atypical carcinoid neuroendocrine tumors. The patient underwent simultaneous neck dissection for bilateral subtotal parathyroidectomy and midline sternotomy for thymectomy of the large mediastinal mass.
MeSH term(s)	Carcinoid Tumor/surgery ; Humans ; Male ; Middle Aged ; Multiple Endocrine Neoplasia Type 1/complications ; Multiple Endocrine Neoplasia Type 1/diagnosis ; Multiple Endocrine Neoplasia Type 1/surgery ; Parathyroidectomy ; Thymectomy ; Thymus Neoplasms/diagnosis ; Thymus Neoplasms/pathology ; Thymus Neoplasms/surgery
Language	English
Publishing date	2021-12-16
Publishing country	Netherlands
Document type	Case Reports
ZDB-ID	211007-6
ISSN	1552-6259 ; 0003-4975
ISSN (online)	1552-6259
ISSN	0003-4975
DOI	10.1016/j.athoracsur.2021.10.065
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Article ; Online: Surgical Repair of Complete Congenital Sternal Cleft Associated With Pectus Excavatum.

Smith, Alexander E P / Mani, Aleksander / Jones, Andrew / Jordan, Simon J

The Annals of thoracic surgery

2019 Volume 109, Issue 1, Page(s) e51–e53

Abstract: Complete congenital cleft sternum associated with pectus excavatum is a rare abnormality. Case reports and case series currently provide the technical standards for comparison in surgical repair. We present a case report of surgical repair of cleft ... ...

Abstract	Complete congenital cleft sternum associated with pectus excavatum is a rare abnormality. Case reports and case series currently provide the technical standards for comparison in surgical repair. We present a case report of surgical repair of cleft sternum and anterior pericardial defect associated with pectus excavatum in a 13-year-old girl. The surgical repair of the cleft sternum and pectus excavatum was performed with a modified Ravitch procedure, closure of the defect with stainless steel wires, and insertion of a pectus bar. Preoperative imaging is important in better defining the defect.
MeSH term(s)	Abnormalities, Multiple/surgery ; Adolescent ; Female ; Funnel Chest/complications ; Funnel Chest/surgery ; Humans ; Musculoskeletal Abnormalities/complications ; Musculoskeletal Abnormalities/surgery ; Orthopedic Procedures/methods ; Sternum/abnormalities ; Sternum/surgery
Language	English
Publishing date	2019-06-14
Publishing country	Netherlands
Document type	Case Reports ; Journal Article
ZDB-ID	211007-6
ISSN	1552-6259 ; 0003-4975
ISSN (online)	1552-6259
ISSN	0003-4975
DOI	10.1016/j.athoracsur.2019.04.079
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Article ; Online: Specific targeting of cytosine methylation to DNA sequences in vivo.

Smith, Alexander E / Ford, Kevin G

Nucleic acids research

2007 Volume 35, Issue 3, Page(s) 740–754

Abstract: Development of methods that will allow exogenous imposition of inheritable gene-specific methylation patterns has potential application in both therapeutics and in basic research. An ongoing approach is the use of targeted DNA methyltransferases, which ... ...

Abstract	Development of methods that will allow exogenous imposition of inheritable gene-specific methylation patterns has potential application in both therapeutics and in basic research. An ongoing approach is the use of targeted DNA methyltransferases, which consist of a fusion between gene-targeted zinc-finger proteins and prokaryotic DNA cytosine methyltransferases. These enzymes however have so far demonstrated significant and unacceptable levels of non-targeted methylation. We now report the development of second-generation targeted methyltransferase enzymes comprising enhanced zinc-finger arrays coupled to methyltransferase mutants that are functionally dominated by their zinc-finger component. Both in vitro plasmid methylation studies and a novel bacterial assay reveal a high degree of target-specific methylation by these enzymes. Furthermore, we demonstrate for the first time transient expression of targeted cytosine methyltransferase in mammalian cells resulting in the specific methylation of a chromosomal locus. Importantly, the resultant methylation pattern is inherited through successive cell divisions.
MeSH term(s)	Base Sequence ; Cytosine/metabolism ; DNA/chemistry ; DNA/metabolism ; DNA Methylation ; DNA-Cytosine Methylases/genetics ; DNA-Cytosine Methylases/metabolism ; Electrophoretic Mobility Shift Assay ; Escherichia coli/genetics ; Genome, Bacterial ; Humans ; Mutagenesis ; Zinc Fingers
Chemical Substances	Cytosine (8J337D1HZY) ; DNA (9007-49-2) ; DNA modification methylase HhaI (EC 2.1.1.-) ; DNA modification methylase HpaII (EC 2.1.1.-) ; DNA-Cytosine Methylases (EC 2.1.1.-)
Language	English
Publishing date	2007
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2205588-5
ISSN	1362-4962 ; 1746-8272 ; 0305-1048 ; 0261-3166
ISSN (online)	1362-4962 ; 1746-8272
ISSN	0305-1048 ; 0261-3166
DOI	10.1093/nar/gkl1053
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Article ; Online: Genetic Analysis of Patients With Sickle Cell Anemia and Stroke Before 4 Years of Age Suggest an Important Role for Apoliprotein E.

Brewin, John N / Smith, Alexander E / Cook, Riley / Tewari, Sanjay / Brent, Julie / Wilkinson, Sarah / Brousse, Valentine / Inusa, Baba / Menzel, Stephan / Rees, David C

Circulation. Genomic and precision medicine

2020 Volume 13, Issue 5, Page(s) 531–540

Abstract: Background: Ischemic stroke is a devastating complication affecting children with sickle cell anemia. Genetic factors are likely to be important in determining the risk of stroke but are poorly defined.: Methods: We have studied a cohort of 19 ... ...

Abstract	Background: Ischemic stroke is a devastating complication affecting children with sickle cell anemia. Genetic factors are likely to be important in determining the risk of stroke but are poorly defined. Methods: We have studied a cohort of 19 children who had an overt ischemic stroke before 4 years of age. We predicted genetic determinants of stroke would be more prominent in this group. We performed whole exome sequencing on this cohort and applied 2 hypotheses to our variant filtering. First, we looked for strong, potentially mono- or oligogenic variants for ischemic stroke, and second, we considered that more common polygenic variants will be enriched in our cohort. Candidate variants emerging from both strategies were validated in a cohort of 283 patients with sickle cell anemia and known pediatric cerebrovascular outcomes. We used principal component analysis in this cohort to control for relatedness and population substructure. Results: Our primary finding was that the Apoliprotein E genotypes ε2/ε4 and ε4/ ε4, defined by the interplay of Conclusions: These data identify new loci for future functional investigations into cerebrovascular disease in sickle cell anemia. Based on African population reference allele frequencies, the Apoliprotein E genotypes would be present in about 10% of children with sickle cell anemia and represent a genetic risk factor that is potentially modifiable by both dietary and pharmaceutical manipulation of its dyslipidemic effects.
MeSH term(s)	Anemia, Sickle Cell/diagnosis ; Anemia, Sickle Cell/genetics ; Apolipoproteins E/genetics ; CX3C Chemokine Receptor 1/genetics ; Child, Preschool ; Collagen Type VII/genetics ; Gene Frequency ; Genotype ; Humans ; Membrane Proteins/genetics ; Multifactorial Inheritance/genetics ; Nerve Tissue Proteins/genetics ; Odds Ratio ; Polymorphism, Single Nucleotide ; Protein Subunits/genetics ; Risk Factors ; Stroke/diagnosis ; Stroke/genetics
Chemical Substances	Apolipoproteins E ; COL7A1 protein, human ; CX3C Chemokine Receptor 1 ; CX3CR1 protein, human ; Collagen Type VII ; Membrane Proteins ; Nerve Tissue Proteins ; Protein Subunits ; TENM3 protein, human
Language	English
Publishing date	2020-09-14
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2574-8300
ISSN (online)	2574-8300
DOI	10.1161/CIRCGEN.120.003025
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Article ; Online: Ectopic humanized mesenchymal niche in mice enables robust engraftment of myelodysplastic stem cells.

Mian, Syed A / Abarrategi, Ander / Kong, Kar Lok / Rouault-Pierre, Kevin / Wood, Henry / Oedekoven, Caroline A / Smith, Alexander E / Batsivari, Antoniana / Ariza-McNaughton, Linda / Johnson, Peter / Snoeks, Thomas / Mufti, Ghulam J / Bonnet, Dominique

Blood cancer discovery

2020 Volume 2, Issue 2, Page(s) 135–145

Abstract: Myelodysplastic syndrome (MDS) are clonal stem cell diseases characterized mainly by ineffective hematopoiesis. Here, we present an approach that enables robust long-term engraftment of primary MDS stem cells (MDS-SCs) in mice by implantation of human ... ...

Abstract	Myelodysplastic syndrome (MDS) are clonal stem cell diseases characterized mainly by ineffective hematopoiesis. Here, we present an approach that enables robust long-term engraftment of primary MDS stem cells (MDS-SCs) in mice by implantation of human mesenchymal cell-seeded scaffolds. Critically for modelling MDS, where patient sample material is limiting, mononuclear bone marrow cells containing as few as 10
MeSH term(s)	Animals ; Bone Marrow Cells ; Hematopoiesis ; Humans ; Mesenchymal Stem Cells ; Mice ; Myelodysplastic Syndromes ; Stem Cells
Language	English
Publishing date	2020-12-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	3028898-8
ISSN	2643-3249 ; 2643-3230
ISSN (online)	2643-3249
ISSN	2643-3230
DOI	10.1158/2643-3230.BCD-20-0161
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Article: Loin to groin pain: The importance of a differential diagnosis.

Smith, Alexander E P / Bhatti, Ibrahim N / Hester, Thomas / Ritchie, James F S

International journal of surgery case reports

2015 Volume 16, Page(s) 122–126

Abstract: Introduction: Ureteric colic frequently presents as loin to groin pain and accounts for a significant proportion of emergency urological admissions. However, a number of differential diagnoses should be considered in a systematic approach when assessing ...

Abstract	Introduction: Ureteric colic frequently presents as loin to groin pain and accounts for a significant proportion of emergency urological admissions. However, a number of differential diagnoses should be considered in a systematic approach when assessing patients. Presentation of case: We report a case of a 30 year old man admitted with severe unilateral loin to groin pain following lumbar specific weightlifting exercises. After a significant delay due to initial mis-diagnosis he was diagnosed with acute paravertebral lumbar compartment syndrome (PVCS) and managed conservatively. Discussion: Exertional PVCS is a rare and potentially life threatening condition arising following lumbar specific exercise that has only been recorded a handful of times previously. Patients typically present with intractable lumbar pain and rhabdomyolysis 6-12h following exercise. Due to initial diagnostic delay our case was managed conservatively with fluid resuscitation and monitoring of renal function. Conclusion: Assessment of patients with loin pain requires a systematic approach. PVCS is a rare cause of lumbar back and loin pain but one that should be considered, particularly in active young males. Early diagnosis is key to prevent the potential sequalae of untreated rhabdomyolysis. There is currently no consensus on management option for PVCS with only a few cases being reported in the literature. We describe successful management with supportive non operative treatment.
Language	English
Publishing date	2015-10-12
Publishing country	Netherlands
Document type	Journal Article
ISSN	2210-2612
ISSN	2210-2612
DOI	10.1016/j.ijscr.2015.09.032
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Article ; Online: Myelodysplastic syndrome can propagate from the multipotent progenitor compartment.

Rouault-Pierre, Kevin / Smith, Alexander E / Mian, Syed A / Pizzitola, Irene / Kulasekararaj, Austin G / Mufti, Ghulam J / Bonnet, Dominique

Haematologica

2017 Volume 102, Issue 1, Page(s) e7–e10

MeSH term(s)	Hematopoietic Stem Cells/metabolism ; Hematopoietic Stem Cells/pathology ; Humans ; Male ; Middle Aged ; Myelodysplastic Syndromes/metabolism ; Myelodysplastic Syndromes/pathology ; Stem Cell Niche
Language	English
Publishing date	2017
Publishing country	Italy
Document type	Case Reports ; Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2016.152520
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Article: Specific targeting of cytosine methylation to DNA sequences in vivo

Smith, Alexander E / Ford, Kevin G

Nucleic acids research. 2007 Feb., v. 35, no. 3

2007

Abstract	Development of methods that will allow exogenous imposition of inheritable gene-specific methylation patterns has potential application in both therapeutics and in basic research. An ongoing approach is the use of targeted DNA methyltransferases, which consist of a fusion between gene-targeted zinc-finger proteins and prokaryotic DNA cytosine methyltransferases. These enzymes however have so far demonstrated significant and unacceptable levels of non-targeted methylation. We now report the development of second-generation targeted methyltransferase enzymes comprising enhanced zinc-finger arrays coupled to methyltransferase mutants that are functionally dominated by their zinc-finger component. Both in vitro plasmid methylation studies and a novel bacterial assay reveal a high degree of target-specific methylation by these enzymes. Furthermore, we demonstrate for the first time transient expression of targeted cytosine methyltransferase in mammalian cells resulting in the specific methylation of a chromosomal locus. Importantly, the resultant methylation pattern is inherited through successive cell divisions.
Keywords	DNA methylation ; cytosine ; loci ; mammals ; methyltransferases ; mutants ; nucleotide sequences ; plasmids ; proteins ; therapeutics
Language	English
Dates of publication	2007-02
Size	p. 740-754.
Document type	Article
ZDB-ID	186809-3
ISSN	0301-5610 ; 0305-1048
ISSN	0301-5610 ; 0305-1048
DOI	10.1093/nar/gkl1053
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Use of altered-specificity binding Oct-4 suggests an absence of pluripotent cell-specific cofactor usage.

Smith, Alexander E F / Ford, Kevin G

Nucleic acids research

2005 Volume 33, Issue 18, Page(s) 6011–6023

Abstract: Oct-4 is a POU domain transcription factor that is critical for maintaining pluripotency and for stem cell renewal. Previous studies suggest that transcription regulation by Oct-4 at particular enhancers requires the input of a postulated E1A-like ... ...

Abstract	Oct-4 is a POU domain transcription factor that is critical for maintaining pluripotency and for stem cell renewal. Previous studies suggest that transcription regulation by Oct-4 at particular enhancers requires the input of a postulated E1A-like cofactor that is specific to pluripotent cells. However, such studies have been limited to the use of enhancer elements that bind other POU-protein family members in addition to Oct-4, thus preventing a 'clean' assessment of any Oct-4:cofactor relationships. Other attempts to study Oct-4 functionality in a more 'stand-alone' situation target Oct-4 transactivation domains to DNA using heterologous binding domains, a methodology which is known to generate artificial data. To circumvent these issues, an altered-specificity binding Oct-4 (Oct-4RR) and accompanying binding site, which binds Oct-4RR only, were generated. This strategy has previously been shown to maintain Oct-1:cofactor interactions that are highly binding-site and protein/binding conformation specific. This system therefore allows a stand-alone study of Oct-4 function in pluripotent versus differentiated cells, without interference from endogenous POU factors and with minimal deviation from bound wild-type protein characteristics. Subsequently, it was demonstrated that Oct-4RR and the highly transactive regions of its N-terminus determined here, and its C-terminus, have the same transactivation profile in pluripotent and differentiated cells, thus providing strong evidence against the existence of such a pluripotent cell-specific Oct-4 cofactor.
MeSH term(s)	Amino Acid Substitution ; Animals ; Binding Sites ; Cell Differentiation ; Cell Line ; Cell Line, Tumor ; DNA/chemistry ; DNA/metabolism ; DNA-Binding Proteins/chemistry ; DNA-Binding Proteins/genetics ; DNA-Binding Proteins/metabolism ; Humans ; Male ; Octamer Transcription Factor-3 ; Pluripotent Stem Cells/metabolism ; Protein Structure, Tertiary ; Transcription Factors/chemistry ; Transcription Factors/genetics ; Transcription Factors/metabolism ; Transcriptional Activation
Chemical Substances	DNA-Binding Proteins ; Octamer Transcription Factor-3 ; POU5F1 protein, human ; Transcription Factors ; DNA (9007-49-2)
Language	English
Publishing date	2005
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2205588-5
ISSN	1362-4962 ; 1746-8272 ; 0305-1048 ; 0261-3166
ISSN (online)	1362-4962 ; 1746-8272
ISSN	0305-1048 ; 0261-3166
DOI	10.1093/nar/gki907
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