Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 531
Filtrar
1.
Histopathology ; 75(6): 825-832, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31236950

RESUMO

AIMS: Pulmonary chondromas, which are rare cartilaginous neoplasms that often arise in the setting of Carney triad, are morphologically similar to pulmonary hamartomas, which are much more common. There is evidence that succinate dehydrogenase (SDH) deficiency drives neoplasia in patients with Carney triad, and SDHB immunohistochemistry can be used as a surrogate marker to detect SDH deficiency. The aim of this study was to investigate the utility of SDHB immunohistochemistry in distinguishing pulmonary chondromas from hamartomas. METHODS AND RESULTS: Immunohistochemistry for SDHB (clone 21A11AE7) was performed on histological sections from six cases of pulmonary chondroma and 33 cases of pulmonary hamartoma. SDHB expression was retained in all 33 pulmonary hamartomas, and lost in the majority of evaluable chondromas (five of six). Of the five patients with chondromas showing SDHB loss, four had definitive Carney triad. Most patients with pulmonary hamartomas were older males with small solitary masses, whereas chondromas often presented as multiple masses in young females. CONCLUSION: Loss of SDHB immunohistochemical expression can be useful for differentiating pulmonary chondromas from hamartomas, and potentially identifying patients with Carney triad.


Assuntos
Condroma/classificação , Hamartoma/classificação , Leiomiossarcoma/classificação , Neoplasias Pulmonares/classificação , Paraganglioma Extrassuprarrenal/classificação , Neoplasias Gástricas/classificação , Succinato Desidrogenase/metabolismo , Condroma/patologia , Feminino , Hamartoma/patologia , Humanos , Imuno-Histoquímica , Leiomiossarcoma/patologia , Neoplasias Pulmonares/patologia , Masculino , Paraganglioma Extrassuprarrenal/patologia , Neoplasias Gástricas/patologia
2.
Transfus Med ; 26(2): 89-98, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26996380

RESUMO

OBJECTIVES: To assess the blood pressure (BP) of donors, the rate of hypertensive range readings amongst donors not previously identified as hypertensive and determine the value of an informational sheet about hypertension given at the time of donation. AIM: To determine the value of screening for high BP during blood donation as a public health activity. BACKGROUND: Blood donation centres measure donor BPs before accepting donations and thus provide a unique opportunity for hypertension screening and education. MATERIALS/METHODS: An anonymous survey was completed by blood donors over 2 weeks. The survey contained 22 questions regarding demographics, BP knowledge and monitoring. Participants then received a hypertension information sheet and assessed its utility with three additional questions. RESULTS: Out of 839 survey responses received, 688 respondents reported their BP in the following categories, normotensive range: 46·9%, pre-hypertensive range: 41·7% and hypertensive range: 11·3%. Notably, of donors with hypertensive range readings, 45% reported no known history of hypertension. After reading the hypertension pamphlet, 63·9% of donors found it valuable, while 38·9% did not. Furthermore, 67% of donors said they were likely to use the information they learned, while 23% of donors said they were unlikely to do so. CONCLUSIONS: An opportunity exists for increasing hypertension awareness during blood donation. Additionally, our findings indicate that an educational pamphlet at the time of donation is valuable to donors. Overall, these findings suggest that increasing hypertension awareness as part of a blood donation screening is not only needed but also useful as a public health measure.


Assuntos
Doadores de Sangue , Pressão Sanguínea , Conhecimentos, Atitudes e Prática em Saúde , Hipertensão , Inquéritos e Questionários , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
3.
Nat Genet ; 38(7): 794-800, 2006 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-16767104

RESUMO

Phosphodiesterases (PDEs) regulate cyclic nucleotide levels. Increased cyclic AMP (cAMP) signaling has been associated with PRKAR1A or GNAS mutations and leads to adrenocortical tumors and Cushing syndrome. We investigated the genetic source of Cushing syndrome in individuals with adrenocortical hyperplasia that was not caused by known defects. We performed genome-wide SNP genotyping, including the adrenocortical tumor DNA. The region with the highest probability to harbor a susceptibility gene by loss of heterozygosity (LOH) and other analyses was 2q31-2q35. We identified mutations disrupting the expression of the PDE11A isoform-4 gene (PDE11A) in three kindreds. Tumor tissues showed 2q31-2q35 LOH, decreased protein expression and high cyclic nucleotide levels and cAMP-responsive element binding protein (CREB) phosphorylation. PDE11A codes for a dual-specificity PDE that is expressed in adrenal cortex and is partially inhibited by tadalafil and other PDE inhibitors; its germline inactivation is associated with adrenocortical hyperplasia, suggesting another means by which dysregulation of cAMP signaling causes endocrine tumors.


Assuntos
Glândulas Suprarrenais/enzimologia , Glândulas Suprarrenais/patologia , Mutação , Diester Fosfórico Hidrolases/genética , 3',5'-GMP Cíclico Fosfodiesterases , Adulto , Criança , Cromossomos Humanos Par 2/genética , Síndrome de Cushing/enzimologia , Síndrome de Cushing/genética , Síndrome de Cushing/patologia , Feminino , Humanos , Hiperplasia , Perda de Heterozigosidade , Masculino , Diester Fosfórico Hidrolases/metabolismo , Polimorfismo de Nucleotídeo Único
4.
Heart Lung Circ ; 23(11): e244-7, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25240574

RESUMO

We report the first case of percutaneous myxoma ablation and retrieval from the right atrium. This novel procedure may reduce the need for repeat surgical excisions in patients with Carney Complex and other recurrent myxoma syndromes.


Assuntos
Complexo de Carney/cirurgia , Ablação por Cateter/métodos , Neoplasias Cardíacas/cirurgia , Mixoma/cirurgia , Adulto , Átrios do Coração/patologia , Átrios do Coração/cirurgia , Neoplasias Cardíacas/patologia , Humanos , Masculino , Mixoma/patologia
5.
J Occup Environ Hyg ; 11(12): 833-9, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24896644

RESUMO

Firefighters are subject to extreme environments and high physical demands when performing duty-related tasks. Recently, physiological status monitors (PSM) have been embedded into a compression shirt to enable firefighters to measure, visualize, log, and transmit vital metrics such as heart rate (HR) to aid in cardiovascular risk identification and mitigation, thereby attempting to improve the health, fitness, and safety of this population. The purpose of this study was to validate HR recorded by the PSM-embedded compression shirt against a criterion standard laboratory ECG-derived HR when worn concurrently with structural firefighting personal protective equipment (PPE) during four simulated firefighting activities. Ten healthy, college-age men (mean ± SD: age: 21 ± 1 yr; body mass: 91 ± 10 kg; body mass index: 26.9 ± 3.1 kg/m(2)) completed four tasks that are routinely performed during firefighting operations: outdoor fast-paced walking (FW), treadmill walking (TW), searching/crawling (SC), and ascending/descending stairs (AD). They wore the PSM-embedded compression shirt under structural firefighting PPE. HR was recorded concurrently by the PSM-embedded compression shirt and a portable metabolic measurement system accompanied with a standard 12-lead electrocardiograph that was used to provide criterion measures of HR. For all four tasks combined there was very high correlation of PSM and ECG HR (r > 0.99; SEE 0.84 /min) with a mean difference (bias) of -0.02 /min and limits of agreement of -0.07 to 0.02 /min. For individual tasks, the correlations were also high (r-values = 0.99; SEE 0.81-0.89). The mean bias (limits of agreement) was: FW 0.03 (-0.09 to 0.14); TW 0.04 (-0.05 to 0.12); SC -0.01 (-0.12 to 0.10); AD -0.13 (-0.21 to -0.04) /min. These findings demonstrate that the PSM-embedded compression shirt provides a valid measure of HR during simulated firefighting activities when compared with a standard 12-lead ECG.


Assuntos
Bombeiros , Frequência Cardíaca , Monitorização Fisiológica/métodos , Esforço Físico , Eletrocardiografia , Humanos , Masculino , Monitorização Fisiológica/instrumentação , Roupa de Proteção , Adulto Jovem
6.
Nat Genet ; 26(1): 89-92, 2000 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-10973256

RESUMO

Carney complex (CNC) is a multiple neoplasia syndrome characterized by spotty skin pigmentation, cardiac and other myxomas, endocrine tumours and psammomatous melanotic schwannomas. CNC is inherited as an autosomal dominant trait and the genes responsible have been mapped to 2p16 and 17q22-24 (refs 6, 7). Because of its similarities to the McCune-Albright syndrome and other features, such as paradoxical responses to endocrine signals, genes implicated in cyclic nucleotide-dependent signalling have been considered candidates for causing CNC (ref. 10). In CNC families mapping to 17q, we detected loss of heterozygosity (LOH) in the vicinity of the gene (PRKAR1A) encoding protein kinase A regulatory subunit 1-alpha (RIalpha), including a polymorphic site within its 5' region. We subsequently identified three unrelated kindreds with an identical mutation in the coding region of PRKAR1A. Analysis of additional cases revealed the same mutation in a sporadic case of CNC, and different mutations in three other families, including one with isolated inherited cardiac myxomas. Analysis of PKA activity in CNC tumours demonstrated a decreased basal activity, but an increase in cAMP-stimulated activity compared with non-CNC tumours. We conclude that germline mutations in PRKAR1A, an apparent tumour-suppressor gene, are responsible for the CNC phenotype in a subset of patients with this disease.


Assuntos
Proteínas Quinases Dependentes de AMP Cíclico/genética , Neoplasias das Glândulas Endócrinas/genética , Mutação , Mixoma/genética , Neoplasias/genética , Neurilemoma/genética , Pigmentação da Pele/genética , Acromegalia/genética , Alelos , Western Blotting , Cromatografia Líquida de Alta Pressão , Cromossomos Humanos Par 17 , Cromossomos Humanos Par 2 , AMP Cíclico/metabolismo , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Análise Mutacional de DNA , DNA Complementar/metabolismo , Éxons , Etiquetas de Sequências Expressas , Saúde da Família , Feminino , Genótipo , Mutação em Linhagem Germinativa , Homozigoto , Humanos , Íntrons , Perda de Heterozigosidade , Masculino , Repetições de Microssatélites , Dados de Sequência Molecular , Ácidos Nucleicos Heteroduplexes , Linhagem , Fenótipo , Polimorfismo Genético
7.
Mod Pathol ; 24(1): 147-51, 2011 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20890271

RESUMO

Mutations in the tumor suppressor genes SDHB, SDHC, and SDHD (or collectively SDHx) cause the inherited paraganglioma syndromes, characterized by pheochromocytomas and paragangliomas. However, other tumors have been associated with SDHx mutations, such as gastrointestinal stromal tumors (GISTs) specifically in the context of Carney-Stratakis syndrome. Previously, we have shown that SDHB immunohistochemistry is a reliable technique for the identification of pheochromocytomas and paragangliomas caused by SDHx mutations. We hypothesized that GISTs in patients with SDHx mutations would be negative immunohistochemically for SDHB as well. Four GISTs from patients with Carney-Stratakis syndrome and six from patients with Carney triad were investigated by SDHB immunohistochemistry. Five GISTs with KIT or PDGFRA gene mutations were used as controls. In addition, SDHB immunohistochemistry was performed on 42 apparently sporadic GISTs. In cases in which the SDHB immunohistochemistry was negative, mutational analysis of SDHB, SDHC, and SDHD was performed. All GISTs from patients with Carney-Stratakis syndrome and Carney triad were negative for SDHB immunohistochemically. In one patient with Carney-Stratakis syndrome, a germline SDHB mutation was found (p.Ser92Thr). The five GISTs with a KIT or PDGFRA gene mutation were all immunohistochemically positive for SDHB. Of the 42 sporadic tumors, one GIST was SDHB-negative. Mutational analysis of this tumor did not reveal an SDHx mutation. All SDHB-negative GISTs were located in the stomach, had an epithelioid morphology, and had no KIT or PDGFRA mutations. We show that Carney-Stratakis syndrome- and Carney-triad-associated GISTs are negative by immunohistochemistry for SDHB in contrast to KIT- or PDGFRA-mutated GISTs and a majority of sporadic GISTs. We suggest that GISTs of epithelioid cell morphology are tested for SDHB immunohistochemically. In case of negative SDHB staining in GISTs, Carney-Stratakis syndrome or Carney triad should be considered and appropriate clinical surveillance should be instituted.


Assuntos
Complexo de Carney/diagnóstico , Tumores do Estroma Gastrointestinal/diagnóstico , Succinato Desidrogenase/metabolismo , Biomarcadores Tumorais/metabolismo , Complexo de Carney/genética , Complexo de Carney/metabolismo , Análise Mutacional de DNA , Células Epitelioides/metabolismo , Células Epitelioides/patologia , Tumores do Estroma Gastrointestinal/genética , Tumores do Estroma Gastrointestinal/metabolismo , Humanos , Imuno-Histoquímica , Mutação , Proteínas Proto-Oncogênicas c-kit/genética , Proteínas Proto-Oncogênicas c-kit/metabolismo , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/genética , Receptor alfa de Fator de Crescimento Derivado de Plaquetas/metabolismo , Succinato Desidrogenase/genética , Síndrome
8.
Anaesthesia ; 66(11): 1023-30, 2011 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-21851346

RESUMO

The extent of analgesia provided by transversus abdominis plane blocks depends upon the site of injection and pattern of spread within the plane. There are currently a number of ultrasound-guided approaches in use, including an anterior oblique-subcostal approach, a mid-axillary approach and a more recently proposed posterior approach. We wished to determine whether the site of injection of local anaesthetic into the transversus abdominis plane affects the spread of the local anaesthetic within that plane, by studying the spread of a local anaesthetic and contrast solution in four groups of volunteers. The first group underwent the classical landmark-based transversus abdominis plane block whereby two different volumes of injectate were studied: 0.3 ml.kg(-1) vs 0.6 ml.kg(-1). The second group underwent transversus abdominis plane block using the anterior subcostal approach. The third group underwent transversus abdominis plane block using the mid-axillary approach. The fourth group underwent transversus abdominis plane block using the posterior approach, in which local anaesthetic was deposited close to the antero-lateral border of the quadratus lumborum. All volunteers subsequently underwent magnetic resonance imaging at 1, 2 and 4 h following each block to determine the spread of local anaesthetic over time. The studies demonstrated that the anterior subcostal and mid-axillary ultrasound approaches resulted in a predominantly anterior spread of the contrast solution within the transversus abdominis plane and relatively little posterior spread. There was no spread to the paravertebral space with the anterior subcostal approach. The mid-axillary transversus abdominis plane block gave faint contrast enhancement in the paravertebral space at T12-L2. In contrast, the posterior approaches, using both landmark and ultrasound identifications, resulted in predominantly posterior spread of contrast around the quadratus lumborum to the paravertebral space from T5 to L1 vertebral levels. We concluded that the pattern of spread of local anaesthetic differs depending on the site of injection into the transversus abdominis plane. This may have important implications for the extent of analgesia produced with each approach.


Assuntos
Parede Abdominal/inervação , Anestésicos Locais/farmacocinética , Bloqueio Nervoso/métodos , Humanos , Masculino
9.
BJS Open ; 5(5)2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34476465

RESUMO

BACKGROUND: Surgical advanced clinical practitioners (SACPs) form part of the extended surgical workforce drawn from a variety of allied healthcare backgrounds. The primary aim of this study was to determine whether there was a financial benefit in having minor surgical procedures undertaken by dedicated SACPs compared with operating lists assigned to consultant surgeons. METHODS: This was a retrospective cohort study including all patients who had minor 'lumps and bumps' procedures undertaken between April 2014 and August 2019 at East Lancashire Hospitals NHS Trust under local anaesthetic by the general surgery team. Clinical patient information, including lesion type, was collected along with operating room staffing levels and duration of operation. The cost of the procedure was calculated as operating time multiplied by cost of staff per minute according to local banding. RESULTS: A total of 1399 patients had a lesion excised; 907 procedures were carried out by a doctor, and the rest independently by a SACP. The majority of lesions excised were lipomas and cysts. There was no difference in the median surgical time taken between SACPs and doctors (20 (i.q.r. 14-28) min). Minor procedures carried out on consultant surgeon lists cost 62.3 per cent (€25.33) more on average than those on SACP lists (median €65.96 versus 40.63 respectively; P < 0.001). CONCLUSION: A dedicated and independent SACP 'lumps and bumps' list was financially beneficial. Operating times were similar to those of doctors. These lists safely free trainee and consultant surgeons to undertake more complex work.


Assuntos
Anestésicos Locais , Cirurgiões , Humanos , Salas Cirúrgicas , Duração da Cirurgia , Estudos Retrospectivos
10.
Hum Mutat ; 31(4): 369-79, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20358582

RESUMO

PRKAR1A encodes the regulatory subunit type 1-alpha (RIalpha) of the cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA). Inactivating PRKAR1A mutations are known to be responsible for the multiple neoplasia and lentiginosis syndrome Carney complex (CNC). To date, at least 117 pathogenic variants in PRKAR1A have been identified (online database: http://prkar1a.nichd.nih.gov). The majority are subject to nonsense mediated mRNA decay (NMD), leading to RIalpha haploinsufficiency and, as a result, activated cAMP signaling. Recently, it became apparent that CNC may be caused not only by RIalpha haploinsufficiency, but also by the expression of altered RIalpha protein, as proven by analysis of expressed mutations in the gene, consisting of amino acid substitutions and in-frame genetic alterations. In addition, a new subgroup of mutations that potentially escape NMD and result in CNC through altered (rather than missing) protein has been analyzed-these are frame-shifts in the 3' end of the coding sequence that shift the stop codon downstream of the normal one. The mutation detection rate in CNC patients is recently estimated at above 60%; PRKAR1A mutation-negative CNC patients are characterized by significant phenotypic heterogeneity. In this report, we present a comprehensive analysis of all presently known PRKAR1A sequence variations and discuss their molecular context and clinical phenotype.


Assuntos
Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/genética , Mutação/genética , Polimorfismo de Nucleotídeo Único/genética , Processamento Alternativo/genética , Complexo de Carney/diagnóstico , Complexo de Carney/enzimologia , Complexo de Carney/genética , Mutação da Fase de Leitura/genética , Estudos de Associação Genética , Humanos , Penetrância , Deleção de Sequência/genética
12.
Anaesthesia ; 65 Suppl 1: 76-83, 2010 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-20377549

RESUMO

In this review, we discuss the central non-neuraxial regional anaesthesia blocks of the abdomen, including intercostal and intrapleural blocks, rectus sheath and ilioinguinal-iliohypogastric blocks, transversus abdominis plane blocks and paravertebral blocks.


Assuntos
Abdome/cirurgia , Bloqueio Nervoso/métodos , Dor Pós-Operatória/prevenção & controle , Parede Abdominal/inervação , Humanos
13.
Ocul Oncol Pathol ; 6(5): 311-317, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33123522

RESUMO

A 74-year-old woman with Carney complex (CNC) and complaints of poor vision was found, on ophthalmic examination, to have a pigmented tumor involving the peripheral choroid and ciliary body in her right eye. The eye was enucleated and showed a ciliochoroidal melanoma with marked pleomorphism. The tumor did not recur or metastasize after almost 10 years of follow-up, and the patient died of unrelated causes. Molecular studies revealed a complex genome with multiple whole-chromosome losses including monosomy of chromosomes 1, 2 (including loss of CNC2at 2p16), 14, 17 (including loss of a copy of PRAKA1 at 17q24.2), 18, 19, 21, 22, and X. No monosomy 3 was observed. This is only the second case of uveal melanoma in a patient with CNC, raising the possibility that this might represent a rare component of this syndrome.

14.
Injury ; 51(6): 1387-1391, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32197830

RESUMO

INTRODUCTION: There are few published studies that investigate the surgical treatment of supination-adduction (SAD, AO/OTA 44A2.3) ankle fractures. The purpose of this study was to describe the complications and outcomes following operative fixation of SAD type 2 ankle fractures. MATERIALS AND METHODS: We identified all SAD-2 ankle fractures that presented at our institution's two hospitals from 2006-2018. Demographics, operative data, and complications (deep infection, superficial infection, delayed union, failure of fixation, and unplanned reoperation) were recorded for all patients. Lastly, all included patients were contacted by telephone for the administration of an 8-question Patient-Reported Outcomes Measurement Information System (PROMIS) Physical Function (PF) and Pain Interference questionnaire (PI). Univariate and multivariate analysis was performed to identify risk factors for complication or poor functional outcome score. RESULTS: 65 patients met inclusion criteria. The average time to surgery was 14 days and average follow-up was 20.5 (range: 0.4-60.9) weeks. There were 9 (13.8%) complications (4 deep infections, 3 superficial infections, 1 delayed union, 1 failure of fixation) and 6 unplanned reoperations. Univariate and multivariate analysis failed to identify any statistically significant risk factors for complication or reoperation. Eleven patients participated in the administration of PROMIS score questionnaires at a mean of 3.4 years postoperatively. The average PROMIS Physical Function T-score was 42.3 ± 11.3 and the average PROMIS Pain Interference T-score was 55.8 ± 7.8. Younger age was associated with a higher physical function score. The use of a direct medial approach to the medial malleolus was associated with a lower pain interference score. CONCLUSION: The overall complication rate for SAD (OTA/AO 44A2.3) type 2 ankle fractures is similar to that of the general ankle fracture population. We were unable to identify risk factors for complication or reoperation. Mean patient reported outcomes are within one standard deviation of the general population. LEVEL OF EVIDENCE: III, retrospective cohort study.


Assuntos
Fraturas do Tornozelo/cirurgia , Articulação do Tornozelo/cirurgia , Fixação Interna de Fraturas/métodos , Complicações Pós-Operatórias/epidemiologia , Adolescente , Adulto , Placas Ósseas , Feminino , Fixação Interna de Fraturas/efeitos adversos , Humanos , Masculino , Pessoa de Meia-Idade , Amplitude de Movimento Articular , Reoperação , Estudos Retrospectivos , Fatores de Risco , Supinação , Ossos do Tarso , Resultado do Tratamento , Adulto Jovem
15.
J Intern Med ; 266(1): 43-52, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19522824

RESUMO

Carney triad (CT) describes the association of paragangliomas (PGLs) with gastrointestinal stromal tumours (GISTs) and pulmonary chondromas (PCH). A number of other lesions have been described in the condition including pheochromocytomas, oesophageal leiomyomas and adrenocortical adenomas; CT is a novel form of multiple endocrine neoplasia (MEN), a genetic condition with a female predilection. Inactivating mutations of the mitochondrial complex II succinate dehydrogenase (SDH) enzyme subunits SDHB, SDHC and SDHD have been found in familial and sporadic PGLs, and gain-of-function mutations of the oncogenes c-kit (KIT) and platelet-derived growth factor receptor A (PDGFRA) cause sporadic and familial GISTs. We recently reported an international series of patients with CT, 34 females and three males (median age of presentation 21 years) who did not carry SDHA, SDHB, SDHC, SDHD, KIT or PDGFRA gene mutations. Comparative genomic hybridization revealed a number of DNA copy number changes. The most frequent and greatest contiguous change was a deletion within the 1pcen13-q21 region, which harbours the SDHC gene. Another frequent change was loss of 1p. Although GISTs showed more frequent losses of 1p than PGLs, the pattern of chromosomal changes was similar in the two tumours despite their different tissue origin and histology; the findings were consistent with a common genetic aetiology of these two tumours in CT. In a separate condition, in which the association (or dyad) of GISTs with PGLs is inherited in an autosomal dominant manner (Carney-Stratakis syndrome, CSS), germline mutations of the SDHB, SDHC and SDHD genes (but not KIT or PDFGRA) were found; GISTs in this condition were caused by SDH deficiency. We conclude that CT is a novel MEN syndrome whose genetic defect remains elusive. CSS is caused by SDH defects, suggesting that sarcomas (GISTs) can be caused by defective mitochondrial oxidation, consistent with recent data implicating this enzyme in a variety of endocrine and other tumours. The above have clinical implications (i) for patients with GISTs that are cKIT- and PDGFRA-mutation negative: these tumours are usually resistant to treatment with currently available tyrosine kinase inhibitors and may be part of a syndrome such as CT or CSS; and (ii) for patients with an inherited PGL syndrome, family history should be explored to identify any other tumours in the family, and in particular other endocrine lesions and GISTs.


Assuntos
Condroma/genética , Tumores do Estroma Gastrointestinal/genética , Neoplasias Pulmonares/genética , Síndromes Neoplásicas Hereditárias/genética , Paraganglioma/genética , Adolescente , Adulto , Criança , Hibridização Genômica Comparativa , Feminino , Humanos , Masculino , Adulto Jovem
16.
J Cell Biol ; 28(2): 375-89, 1966 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-5914697

RESUMO

The morphology of the canine cardiac myosin molecule has been investigated in the electron microscope with Hall's mica-replica technique. The molecule is an elongated rod (shaft) of nonuniform diameter with a globular expansion (head) on one end. Statistical analysis of the lengths of 1908 molecules showed that the mean length was 1610 +/- 250 A; the mean length of the head was 210 +/- 20 A; and the diameter of the head and that of the shaft were 35 to 40 and 15 to 20 A, respectively. About one-third of the molecules had single or multiple, fairly sharp, angulations along their shafts. Rarely, some details of the substructure of the molecule have been observed. Large, spindle-shaped aggregates, measuring 0.5 to 1 micro in length and 50 to 100 A in diameter, were produced by dilution of the myosin solutions. These aggregates were readily visualized in the electron microscope by means of Huxley's negative-staining technique. Projections often were visible along the length of the aggregates except at a central zone where they were frequently absent. The aggregates resembled the thick myofilaments of the myocardium and appeared similar to those produced by Huxley from skeletal myosin solutions.


Assuntos
Proteínas Musculares/análise , Miocárdio/análise , Animais , Cães , Microscopia Eletrônica , Ultracentrifugação
17.
Science ; 199(4331): 845-51, 1978 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-17757569

RESUMO

We used a detailed engineering-economic simulation model of residential energy use to evaluate the effects of nine different residential energy-use "futures." These "futures" are described in terms of annual and cumulative energy use from 1977 through 2000 by fuel, end use, and in aggregate. Outputs from the model also include economic information on the costs to households of fuels, equipment, and thermal improvements to new and existing structures. The major outputs from these nine cases are shown in Tables 1 and 2 and Figs. 6 and 7.

18.
Science ; 287(5453): 640-2, 2000 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-10649995

RESUMO

The polyketide epothilone is a potential anticancer agent that stabilizes microtubules in a similar manner to Taxol. The gene cluster responsible for epothilone biosynthesis in the myxobacterium Sorangium cellulosum was cloned and completely sequenced. It encodes six multifunctional proteins composed of a loading module, one nonribosomal peptide synthetase module, eight polyketide synthase modules, and a P450 epoxidase that converts desoxyepothilone into epothilone. Concomitant expression of these genes in the actinomycete Streptomyces coelicolor produced epothilones A and B. Streptomyces coelicolor is more amenable to strain improvement and grows about 10-fold as rapidly as the natural producer, so this heterologous expression system portends a plentiful supply of this important agent.


Assuntos
Proteínas de Bactérias , Sistema Enzimático do Citocromo P-450/genética , Epotilonas , Compostos de Epóxi/metabolismo , Complexos Multienzimáticos/genética , Família Multigênica , Oxirredutases/genética , Tiazóis/metabolismo , Clonagem Molecular , Cosmídeos , Sistema Enzimático do Citocromo P-450/metabolismo , Fermentação , Genes Bacterianos , Dados de Sequência Molecular , Complexos Multienzimáticos/metabolismo , Myxococcales/genética , Óperon , Oxirredutases/metabolismo , Proteínas Recombinantes/biossíntese , Streptomyces/genética , Streptomyces/metabolismo , Transformação Genética
19.
Clin Cancer Res ; 14(2): 388-95, 2008 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-18223213

RESUMO

PURPOSE: Since the identification of PRKAR1A mutations in Carney complex, substitutions and small insertions/deletions have been found in approximately 70% of the patients. To date, no germ-line PRKAR1A deletion and/or insertion exceeded a few base pairs (up to 15). Although a few families map to chromosome 2, it is possible that current sequencing techniques do not detect larger gene changes in PRKAR1A -- mutation-negative individuals with Carney complex. EXPERIMENTAL DESIGN: To screen for gross alterations of the PRKAR1A gene, we applied Southern hybridization analysis on 36 unrelated Carney complex patients who did not have small intragenic mutations or large aberrations in PRKAR1A, including the probands from two kindreds mapping to chromosome 2. RESULTS: We found large PRKAR1A deletions in the germ-line of two patients with Carney complex, both sporadic cases; no changes were identified in the remaining patients, including the two chromosome-2-mapping families. In the first patient, the deletion is expected to lead to decreased PRKAR1A mRNA levels but no other effects on the protein; the molecular phenotype is predicted to be PRKAR1A haploinsufficiency, consistent with the majority of PRKAR1A mutations causing Carney complex. In the second patient, the deletion led to in-frame elimination of exon 3 and the expression of a shorter protein, lacking the primary site for interaction with the catalytic protein kinase A subunit. In vitro transfection studies of the mutant PRKAR1A showed impaired ability to bind cyclic AMP and activation of the protein kinase A enzyme. The patient bearing this mutation had a more-severe-than-average Carney complex phenotype that included the relatively rare psammomatous melanotic schwannoma. CONCLUSIONS: Large PRKAR1A deletions may be responsible for Carney complex in patients that do not have PRKAR1A gene defects identifiable by sequencing. Preliminary data indicate that these patients may have a different phenotype especially if their defect results in an expressed, abnormal version of the PRKAR1A protein.


Assuntos
Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/genética , Deleção de Genes , Neoplasia Endócrina Múltipla/genética , Linhagem Celular , Subunidade RIalfa da Proteína Quinase Dependente de AMP Cíclico/metabolismo , Éxons , Humanos
20.
Br J Anaesth ; 102(1): 128-34, 2009 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19059923

RESUMO

BACKGROUND: The Pentax Airwayscope, the Glidescope, and the Truview EVO2 constitute three novel laryngoscopes that facilitate visualization of the vocal cords without alignment of the oral, pharyngeal, and tracheal axes. We compared these devices with the Macintosh laryngoscope in a simulated easy and difficult laryngoscopy. METHODS: Thirty-five experienced anaesthetists were allowed up to three attempts to intubate in each of four laryngoscopy scenarios in a Laerdal SimMan manikin. The time required to perform tracheal intubation, the success rate, number of intubation attempts and of optimization manoeuvres, and the severity of dental compression were recorded. RESULTS: In the simulated easy laryngoscopy scenarios, there was no difference between the study devices and the Macintosh in success of tracheal intubation. In more difficult tracheal intubation scenarios, the Glidescope and Pentax AWS, and to a lesser extent the Truview EVO2 laryngoscope demonstrated advantages over the Macintosh laryngoscope including a better view of the glottis, greater success of tracheal intubation, and ease of device use. The Pentax AWS was more successful in achieving tracheal intubation, required less time to successfully perform tracheal intubation, caused less dental trauma, and was considered by the anaesthetists to be easier to use. CONCLUSIONS: The Pentax AWS laryngoscope demonstrated more advantages over the Macintosh laryngoscope than either the Truview EVO2 or the Glidescope laryngoscope, when used by experienced anaesthetists in difficult tracheal intubation scenarios.


Assuntos
Laringoscópios , Anestesiologia/normas , Vértebras Cervicais , Competência Clínica , Estudos Cross-Over , Edema/complicações , Desenho de Equipamento , Imobilização , Intubação Intratraqueal/instrumentação , Intubação Intratraqueal/métodos , Laringoscopia/métodos , Manequins , Doenças da Língua/complicações
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA