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1.
Psychol Med ; 47(7): 1179-1191, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27998319

RESUMO

BACKGROUND: The public health, public safety and clinical implications of violent events among adults with mental illness are significant; however, the causes and consequences of violence and victimization among adults with mental illness are complex and not well understood, which limits the effectiveness of clinical interventions and risk management strategies. This study examined interrelationships between violence, victimization, psychiatric symptoms, substance use, homelessness and in-patient treatment over time. METHOD: Available data were integrated from four longitudinal studies of adults with mental illness. Assessments took place at baseline, and at 1, 3, 6, 9, 12, 15, 18, 24, 30 and 36 months, depending on the parent studies' protocol. Data were analysed with the autoregressive cross-lag model. RESULTS: Violence and victimization were leading indicators of each other and affective symptoms were a leading indicator of both. Drug and alcohol use were leading indicators of violence and victimization, respectively. All psychiatric symptom clusters - affective, positive, negative, disorganized cognitive processing - increased the likelihood of experiencing at least one subsequent symptom cluster. Sensitivity analyses identified few group-based differences in the magnitude of effects in this heterogeneous sample. CONCLUSIONS: Violent events demonstrated unique and shared indicators and consequences over time. Findings indicate mechanisms for reducing violent events, including trauma-informed therapy, targeting internalizing and externalizing affective symptoms with cognitive-behavioral and psychopharmacological interventions, and integrating substance use and psychiatric care. Finally, mental illness and violence and victimization research should move beyond demonstrating concomitant relationships and instead focus on lagged effects with improved spatio-temporal contiguity.


Assuntos
Vítimas de Crime/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Pessoas Mal Alojadas/estatística & dados numéricos , Transtornos Mentais/epidemiologia , Violência/estatística & dados numéricos , Adulto , Humanos , Transtornos Mentais/terapia
2.
Eur Psychiatry ; 31: 13-9, 2016 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-26657597

RESUMO

Phase 1 of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) study enrolled a sample of 1493 chronic schizophrenia patients. The European First Episode Schizophrenia Trial (EUFEST) enrolled 498 patients. We have combined these two samples to study the effects of hostility on study discontinuation as well as to examine correlates and predictors of hostility. Individual data from 1154 patients with complete data were used for analyses. Survival analysis demonstrated that higher hostility was associated with earlier all-cause treatment discontinuation. Furthermore, regression analysis indicated that increased hostility was associated with more severe positive symptoms, lower adherence to pharmacological treatment, younger age, impaired insight, and more drug or alcohol consumption. The clinical implications of the results point to the importance of establishing therapeutic alliance while managing patient's symptoms of hostility with antipsychotics such as olanzapine combined with psychosocial interventions to improve insight and reduce substance use.


Assuntos
Antipsicóticos/uso terapêutico , Hostilidade , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Adulto , Benzodiazepinas/administração & dosagem , Ensaios Clínicos como Assunto , Europa (Continente) , Feminino , Humanos , Modelos Logísticos , Masculino , Adesão à Medicação/psicologia , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Olanzapina , Valor Preditivo dos Testes , Projetos de Pesquisa , Índice de Gravidade de Doença , Resultado do Tratamento
3.
Nuklearmedizin ; 52(1): 1-6, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23192295

RESUMO

UNLABELLED: The clinical significance of (18)F-FDG-PET/CT in the follow-up of patients with differentiated thyroid carcinoma was evaluated and the results were compared with those of (18)F-FDG-PET, (131)I-whole-body scintigraphy including SPECT/CT (WBS) and ultrasound. In addition, it was the aim to investigate the impact of (18)F-FDG-PET/CT on the therapeutic management. PATIENTS, METHODS: 327 patients (209 women, 118 men; mean age 53 ± 18 years) with differentiated thyroid cancer (242 papillary, 75 follicular, 6 mixed, 1 Hürthle cell and 3 poorly differentiated tumours) were analyzed retrospectively at four tertiary referral centres. 289 (18)F-FDG-PET/CT and 118 (18)F-FDG-PET studies were performed in these patients between 2007 and 2010. In addition, an overall clinical evaluation was performed, including cytology, histology, thyroglobulin level, ultrasound, WBS, and subsequent clinical course in order to compare the molecular imaging results. Finally, the change in therapeutic management due to findings of (18)F-FDG-PET/CT was investigated. RESULTS: The sensitivity of (18)F-FDG-PET/CT was 92%, the specificity was 95%. Sensitivity and specificity of (18)F-FDG-PET alone were 67% and 93%, respectively. WBS showed a sensitivity of 65% and a specificity of 94%. The corresponding values of ultrasound were 37% and 94%, respectively. The sensitivity of (18)F-FDG-PET/CT in the group of patients with a negative WBS (n=194) amounted to 96%. When (18)F-FDG-PET/CT and WBS were considered in combination, tumour tissue was missed in only 2 out of 133 patients; when (18)F-FDG-PET and WBS were combined, tumour tissue was missed in 1 out of 24 patients. (18)F-FDG-PET/CT resulted in management change in 43% (n=57/133) with a decision on surgical approach in 20% (n=27/133). CONCLUSIONS: (18)F-FDG-PET/CT is superior to (18)F-FDG-PET alone in patients with differentiated thyroid cancer and has a direct impact on the therapeutic management of patients with suspected local recurrence or metastases, particularly in those with negative WBS.


Assuntos
Fluordesoxiglucose F18 , Imagem Multimodal/estatística & dados numéricos , Tomografia por Emissão de Pósitrons , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/terapia , Tomografia Computadorizada por Raios X , Feminino , Alemanha/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Fatores de Risco , Neoplasias da Glândula Tireoide/epidemiologia , Resultado do Tratamento
4.
Eur J Nucl Med Mol Imaging ; 36(9): 1377-82, 2009 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-19430782

RESUMO

PURPOSE: Sentinel lymph node dissection (SLND) has replaced extended lymphadenectomy for nodal staging in several solid tumours. We present our results of SLND in prostate cancer in regard to detection and false-negative rate. METHODS: In a 2-day protocol about 300 MBq (99m)Tc-nanocolloid are injected into the prostate. Two hours later static scans of the pelvis are performed to get information about the number and location of radioactive lymph nodes. During surgery the radioactive nodes are excised with the help of a gamma probe and sent separately to the pathologist. The histological procedure includes haematoxylin and eosin staining, serial sections and immunohistochemistry. RESULTS: Since 1999, a total of 2,020 men underwent SLND alone or in combination with either standard or extended lymphadenectomy after radical retropubic prostatectomy. Lymph nodes positive for metastases were found in 16.7% of patients. The scintigraphic detection rate was 97.6% and the intraoperative detection rate 98%. For 187 lymph node-positive men who had either standard or extended lymphadenectomy in addition to SLND the false-negative rate could be calculated, resulting in false-negative findings in 11 of 187 patients (6%). CONCLUSION: Our results demonstrate that SLND in prostate cancer is a reliable procedure for nodal staging.


Assuntos
Excisão de Linfonodo , Neoplasias da Próstata/patologia , Reações Falso-Negativas , Humanos , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Linfonodos/cirurgia , Metástase Linfática , Masculino , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/cirurgia , Cintilografia , Compostos Radiofarmacêuticos , Tecnécio
5.
Nuklearmedizin ; 47(5): 216-9, 2008.
Artigo em Alemão | MEDLINE | ID: mdl-18852929

RESUMO

AIM: We investigated the influence of the injection technique on the false negative rate in identifying the sentinel lymph node in multifocal breast cancer. PATIENTS, METHODS: 958 consecutive patients were divided into unifocal and multifocal breast cancer patients. The scintigrafic and intraoperative detection rate as well as the false negatives were calculated in relation to peritumoral or subareolar injection. RESULTS: In all patients the scintigrafic and intraoperative detection rate exceeded 99%, except in patients with multifocal cancer, who were injected peritumorally. In this group the intraoperative detection rate declined to 96%. In patients with unifocal breast cancer the false negative rate was below 5%, independent of the injection technique. Multifocal breast cancer patients showed a significant dependence on the injection technique. The false negative rate was 26.3% in patients with peritumoral injection and 5.6% in those with subareolar injection. CONCLUSION: The results clearly demonstrate that in multifocal breast cancer a reliable detection of a SLN is impossible with the peritumoral injection technique. Subareolar injection seems to be a way to operate on multifocal breast cancer with SLNE, but the number of investigated patients is too low for statistic approval. So, prospective studies should be performed to validate these preliminary results before SLNE becomes routine in multifocal breast cancer.


Assuntos
Neoplasias da Mama Masculina/diagnóstico por imagem , Neoplasias da Mama/diagnóstico por imagem , Axila , Biópsia , Neoplasias da Mama/patologia , Neoplasias da Mama/cirurgia , Neoplasias da Mama Masculina/patologia , Neoplasias da Mama Masculina/cirurgia , Reações Falso-Negativas , Feminino , Humanos , Excisão de Linfonodo , Masculino , Monitorização Intraoperatória , Cintilografia
6.
Neuroscience ; 153(2): 461-73, 2008 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-18400405

RESUMO

Basic fibroblast growth factor (FGF-2) is up-regulated in response to a nerve lesion and promotes axonal regeneration by activation of the tyrosine kinase receptor fibroblast growth factor receptor 1 (FGFR1). To determine the effects of elevated FGFR1 levels on neurite outgrowth, overexpression was combined with lysosomal inhibition of receptor degradation. In pheochromocytoma (PC12) cells, FGFR1 overexpression resulted in flattened morphology, increased neurite outgrowth and activation of extracellular signal-regulated kinase (ERK) and AKT. Degradation of FGFR1 was inhibited by the lysosomal inhibitor leupeptin and by the proteasomal inhibitor lactacystin. In rat primary adult neurons, FGFR1 overexpression enhanced FGF-2-induced axon growth which was further increased by co-treatment with leupeptin. Lysosomal inhibition of receptor degradation concomitant with ligand stimulation of neurons overexpressing FGFR1 provides new insight in tyrosine kinase receptor-mediated promotion of axon regeneration and demonstrates that adult sensory neurons express sub-optimal levels of tyrosine kinase receptors for neurotrophic factors.


Assuntos
Lisossomos/fisiologia , Neuritos/fisiologia , Feocromocitoma/metabolismo , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/fisiologia , Células Receptoras Sensoriais/metabolismo , Acetilcisteína/análogos & derivados , Acetilcisteína/farmacologia , Animais , Western Blotting , Inibidores de Cisteína Proteinase/farmacologia , Fatores de Crescimento de Fibroblastos/farmacologia , Gânglios Espinais/citologia , Gânglios Espinais/efeitos dos fármacos , Proteínas de Fluorescência Verde/química , Leupeptinas/farmacologia , Ligantes , Lisossomos/efeitos dos fármacos , Células PC12 , Ratos , Receptor Tipo 1 de Fator de Crescimento de Fibroblastos/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/fisiologia
7.
Biodegradation ; 19(3): 347-63, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-17636392

RESUMO

The aerobic polyaromatic hydrocarbon (PAH) degrading microbial communities of two petroleum-impacted Spartina-dominated salt marshes in the New York/New Jersey Harbor were examined using a combination of microbiological, molecular and chemical techniques. Microbial isolation studies resulted in the identification of 48 aromatic hydrocarbon-degrading bacterial strains from both vegetated and non-vegetated marsh sediments. The majority of the isolates were from the genera Paenibacillus and Pseudomonas. Radiotracer studies using (14)C-phenanthrene and (14)C-pyrene were used to measure the PAH-mineralization activity in salt marsh sediments. The results suggested a trend towards increased PAH mineralization in vegetated sediments relative to non-vegetated sediments. This trend was supported by the enumeration of PAH-degrading bacteria in non-vegetated and vegetated sediment using a Most Probable Numbers (MPN) technique, which demonstrated that PAH-degrading bacteria existed in non-vegetated and vegetated sediments at levels ranging from 10(2 )to 10(5 )cells/g sediment respectively. No difference between microbial communities present in vegetated versus non-vegetated sediments was found using terminal restriction fragment length polymorphism (of the 16S rRNA gene) or phospholipid fatty acid analysis. These studies provide information on the specific members and activity of the PAH-degrading aerobic bacterial communities present in Spartina-dominated salt marshes in the New York/New Jersey Harbor estuary.


Assuntos
Bactérias/metabolismo , Gleiquênias/metabolismo , Hidrocarbonetos/metabolismo , Cloreto de Sódio , Áreas Alagadas , Bactérias/genética , New Jersey , New York , Filogenia , Água do Mar
8.
Nuklearmedizin ; 45(3): 101-4, 2006.
Artigo em Alemão | MEDLINE | ID: mdl-16710504

RESUMO

AIM: In combined focal and disseminated thyroid autonomy a variety of concepts in the treatment with radioiodine are used. The difference lies mainly in the calculation of the autonomous volume. This retrospective study shows a new method of calculating the autonomous volume. PATIENTS AND METHODS: In 398 patients with combined thyroid autonomy and good correlation of scintigraphically hot nodules and lesions defined by ultrasound the volume of the nodules is ascertained from scintigraphic and ultrasound parameters and the volume of the disseminated autonomous tissue is assessed with a weighting factor (VF). This factor is the ratio of impulse density in a ROI over the disseminated volume divided by the corresponding impulse density over the nodular volume of the thyroid scintigraphy. The sum of nodular volume and weighted perinodular volume gives the total autonomous volume. A standard radioiodine test gives the maximum iodine-131-uptake and effective half-life to calculate the activity to obtain a treatment dose of 400 Gy. RESULTS: The rate of success with and without thyrostatic medication was 97% with an 18.6% rate of hypothyroidism observed from 4 months post therapy onwards. CONCLUSION: The use of the weighting factor VF in the treatment of combined autonomy leads to an excellent rate of success in patients with good correlation of functional imaging and ultrasound findings.


Assuntos
Radioisótopos do Iodo/uso terapêutico , Nódulo da Glândula Tireoide/radioterapia , Humanos , Cintilografia , Dosagem Radioterapêutica , Estudos Retrospectivos , Nódulo da Glândula Tireoide/diagnóstico por imagem , Resultado do Tratamento
9.
Urologe A ; 45(6): 723-7, 2006 Jun.
Artigo em Alemão | MEDLINE | ID: mdl-16586052

RESUMO

There is no consensus on which prostate cancer patients should undergo lymph node removal and which lymph nodes should be included. Therefore, most clinicians rely on nomograms and dispense with lymph node dissection in patients with low-risk disease. Meanwhile, there are some studies which prove that there are also lymph node metastases in patients with low-risk prostate cancer and that lymph node metastases are predominantly localized outside the region of standard lymphadenectomy. In more than 800 men we could show that lymph node metastases were found more often than shown in the Partin tables. These lymph node metastases were detected by sentinel lymph node dissection outside the region of standard and extended lymphadenectomy. Because of insufficient preoperative diagnostics it is unclear which patients have positive lymph nodes. Therefore, it is useful to perform lymph node dissection in every patient. Men with positive nodes could have a better prognosis, when sentinel and extended lymph node dissection are performed.


Assuntos
Excisão de Linfonodo , Neoplasias da Próstata/cirurgia , Biópsia de Linfonodo Sentinela , Biomarcadores Tumorais/sangue , Humanos , Linfonodos/patologia , Metástase Linfática/patologia , Masculino , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Próstata/patologia , Antígeno Prostático Específico/sangue , Prostatectomia , Neoplasias da Próstata/patologia , Glândulas Seminais/patologia , Bexiga Urinária/patologia
10.
Phys Rev Lett ; 91(23): 233901, 2003 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-14683185

RESUMO

We experimentally demonstrate for the first time that a radially polarized field can be focused to a spot size significantly smaller [0.16(1)lambda(2)] than for linear polarization (0.26lambda(2)). The effect of the vector properties of light is shown by a comparison of the focal intensity distribution for radially and azimuthally polarized input fields. For strong focusing, a radially polarized field leads to a longitudinal electric field component at the focus which is sharp and centered at the optical axis. The relative contribution of this component is enhanced by using an annular aperture.

11.
Med Biol Eng Comput ; 41(2): 172-82, 2003 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-12691437

RESUMO

The long-term ST database is the result of a multinational research effort. The goal was to develop a challenging and realistic research resource for development and evaluation of automated systems to detect transient ST segment changes in electrocardiograms and for supporting basic research into the mechanisms and dynamics of transient myocardial ischaemia. Twenty-four hour ambulatory ECG records were selected from routine clinical practice settings in the USA and Europe, between 1994 and 2000, on the basis of occurrence of ischaemic and non-ischaemic ST segment changes. Human expert annotators used newly developed annotation protocols and a specially developed interactive graphic editor tool (SEMIA) that supported paperless editing of annotations and facilitated international co-operation via the Internet. The database contains 86 two- and three-channel 24 h annotated ambulatory records from 80 patients and is stored on DVD-ROMs. The database annotation files contain ST segment annotations of transient ischaemic (1155) and heart-rate related ST episodes and annotations of non-ischaemic ST segment events related to postural changes and conduction abnormalities. The database is intended to complement the European Society of Cardiology ST-T database and the MIT-BIH and AHA arrhythmia databases. It provides a comprehensive representation of 'real-world' data, with numerous examples of transient ischaemic and non-ischaemic ST segment changes, arrhythmias, conduction abnormalities, axis shifts, noise and artifacts.


Assuntos
Bases de Dados Factuais , Eletrocardiografia Ambulatorial , Isquemia Miocárdica/diagnóstico , Adulto , Idoso , Idoso de 80 Anos ou mais , Europa (Continente) , Feminino , Humanos , Cooperação Internacional , Masculino , Pessoa de Meia-Idade , Estados Unidos
12.
Nuklearmedizin ; 41(2): 102-7, 2002 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-11989296

RESUMO

AIM: To visualise the sentinel lymph nodes (SLNs) of the prostate we injected the radiotracer into the parenchyma of the prostate. The activity was deposited in liver, spleen, bone marrow, urinary bladder and regional lymphatic system. The aim of this work is to determine biokinetical data and to estimate radiation doses to the patient. METHODS: The patients with prostate cancer received a sonographically controlled, transrectal administration of 99mTc-Nanocoll, injected directly into both prostate lobes. In 10 randomly selected patients radionuclide distribution and its time course was determined via regions of interest (ROIs) over prostate, urinary bladder, liver, spleen and the lymph nodes. The uptake in the SLNs was estimated from gamma probe measurements at the surgically removed nodes. To compare tumour positive with tumour free lymph nodes according to SLN-uptake and SLN-localisation we evaluated 108 lymph nodes out of 24 patients with tumour positive SLN. For calculating the effective dose according to ICRP 60 of the patients we used the MIRD-method and the Mirdose 3.1 software. RESULTS: The average uptake of separate organs was: bladder content 24%, liver 25.5%, spleen 2%, sum of SLN 0.5%. An average of 9% of the applied activity remained in the prostate. The residual activity was mainly accumulated in bone marrow and blood. Occasionally a weak activity enrichment in intestinal tract and kidneys could be recognized. The effective dose to the patient was estimated to 7.6 microSv/MBq. The radioactivity uptake of the SLN varied in several orders of magnitude between 0.006% and 0.6%. The probability of SLN-metastasis was found to be independent from tracer uptake in the lymph node. The radioactivity uptake of the SLNs in distinct lymph node regions showed no significant differences. CONCLUSION: The radiotracer is transferred out of the prostate via blood flow, by direct transfer via the urethra into the bladder and by lymphatic transport. Injecting a total activity of 200 MBq leads to a mean effective dose of 1.5 mSv. It is not recommended to use the tracer uptake in lymph nodes as the only criterion to characterize SLNs.


Assuntos
Metástase Linfática/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Compostos Radiofarmacêuticos , Biópsia de Linfonodo Sentinela , Agregado de Albumina Marcado com Tecnécio Tc 99m , Transporte Biológico , Humanos , Injeções , Masculino , Especificidade de Órgãos , Neoplasias da Próstata/patologia , Cintilografia , Compostos Radiofarmacêuticos/administração & dosagem , Compostos Radiofarmacêuticos/farmacocinética , Reprodutibilidade dos Testes , Agregado de Albumina Marcado com Tecnécio Tc 99m/administração & dosagem , Agregado de Albumina Marcado com Tecnécio Tc 99m/farmacocinética , Distribuição Tecidual
13.
Nuklearmedizin ; 41(2): 95-101, 2002 Apr.
Artigo em Alemão | MEDLINE | ID: mdl-11989304

RESUMO

AIM: Evaluation of the significance of lymphoscintigraphy and intraoperative probe measurement for the identification of the sentinel lymph node (SLN) in prostate cancer. PATIENTS AND METHOD: In 117 patients with prostate cancer scintigrams in various projections were acquired till approximately 6 hours p.i. after ultrasound guided transrectal intraprostatic injection of 99mTc-Nanocoll. On the following day the SLNs were identified in the operation theatre with a gamma probe and removed. Pelvic standard lymph node dissection followed SLNE. RESULTS: In three of 117 patients with preoperative lymphoscintigraphy no SLN was scintigraphically detectable. These three patients had antecedent transurethral resection of the prostate. In 113 of the residual 114 patients SLN could be intraoperatively localized. In the mean four SLNs per patient were removed. 28 of 117 patients had pelvic lymph node metastases. In 25 cases SLN were right-positive, in one false-negative and in one intraoperatively not detectable. In one patient we found macrometastasis of up to 4 cm diameter (one SLN was tumour positive). In 15 cases only the SLN was bearing tumour. CONCLUSION: The SLNE with preoperative lymphoscintigraphy and intraoperative gamma probe measurement is suitable for detecting lymph node metastasis in prostate cancer. SLNE is superior to the surgical techniques commonly used in pelvic lymphadenectomy.


Assuntos
Metástase Linfática/diagnóstico por imagem , Neoplasias da Próstata/diagnóstico por imagem , Biópsia de Linfonodo Sentinela , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias da Próstata/patologia , Cintilografia , Compostos Radiofarmacêuticos , Reprodutibilidade dos Testes , Agregado de Albumina Marcado com Tecnécio Tc 99m
14.
Violence Vict ; 16(4): 371-88, 2001 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-11506447

RESUMO

The study examines the extent to which gender, personality attributes, household, community, and environmental factors are associated with violent behaviors in young adulthood. The authors present findings from a sample of 765 21-year-old individuals participating in a drug and delinquency prevention study. Personality attributes, opportunities, and social acceptability of antisocial behaviors were identified as accounting for gender differences and having more influence on violent behavior than environmental correlates. Implications for preventive intervention are discussed.


Assuntos
Comportamento do Adolescente/psicologia , Violência/psicologia , Adolescente , Adulto , Violência Doméstica/psicologia , Feminino , Humanos , Acontecimentos que Mudam a Vida , Masculino , Mudança Social , Meio Social
15.
Proc Natl Acad Sci U S A ; 98(17): 9724-9, 2001 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-11493677

RESUMO

The Drosophila BTB domain containing gene mod(mdg4) produces a large number of protein isoforms combining a common N-terminal region of 402 aa with different C termini. We have deduced the genomic structure of this complex locus and found that at least seven of the mod(mdg4) isoforms are encoded on both of its antiparallel DNA strands, suggesting the generation of mature mRNAs by trans-splicing. In transgenic assays, we demonstrate the ability of Drosophila to produce mod(mdg4) mRNAs by trans-splicing of pre-mRNAs generated from transgenes inserted at distant chromosomal positions. Furthermore, evidence is presented for occurring of trans-splicing of mod(mdg4)-specific exons encoded by the parallel DNA strand. The mod(mdg4) locus represents a new type of complex gene structure in which genetic complexity is resolved by extensive trans-splicing, giving important implications for genome sequencing projects. Demonstration of naturally occurring trans-splicing in the model organism Drosophila opens new experimental approaches toward an analysis of the underlying mechanisms.


Assuntos
Proteínas de Drosophila , Drosophila melanogaster/genética , Proteínas de Insetos/genética , Isoformas de Proteínas/genética , Splicing de RNA , RNA Mensageiro/metabolismo , Fatores de Transcrição/genética , Transgenes , Sequência de Aminoácidos , Animais , Sequência de Bases , DNA Complementar/genética , Éxons/genética , Proteínas de Insetos/biossíntese , Íntrons/genética , Modelos Genéticos , Dados de Sequência Molecular , Isoformas de Proteínas/biossíntese , Proteínas Recombinantes de Fusão/biossíntese , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Alinhamento de Sequência , Homologia de Sequência de Aminoácidos , Fatores de Transcrição/biossíntese
17.
J Endocrinol Invest ; 24(2): 111-5, 2001 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-11263468

RESUMO

Riedel's thyroiditis is a rare disease determined by an invasive fibrosclerotic transformation of the thyroid gland. It may be one manifestation of multifocal fibrosis with still unknown etiology. Because it mimics carcinoma, a biopsy must be performed to get the correct diagnosis. The condition is self-limiting when confined to the neck. Prognosis depends on the extent of extracervical fibrosclerosis. We present a patient with a huge cervical and mediastinal, unilateral thyroid mass expanding to the aortic curve, which led to tracheal deviation and compression with symptoms of stridor and dyspnea. These symptoms continued under a course of high-dose steroids; thus an operation was necessary to relieve the airway obstruction and limit inflammation. Intraoperative and pathological findings showed an inflammatory infiltration of the adjacent neck muscles and a sterile abscess caused by an occlusive vasculitis. Therefore, hemithyroidectomy had to be performed instead of a local limited resection.


Assuntos
Abscesso/etiologia , Glândula Tireoide/patologia , Tireoidite/complicações , Tireoidite/diagnóstico , Vasculite/complicações , Idoso , Fibrose , Humanos , Linfócitos/patologia , Imageamento por Ressonância Magnética , Masculino , Neutrófilos/patologia , Plasmócitos/patologia , Esclerose , Tireoidectomia , Tireoidite/patologia
19.
Genetics ; 155(1): 141-57, 2000 May.
Artigo em Inglês | MEDLINE | ID: mdl-10790390

RESUMO

mod(mdg4), also known as E(var)3-93D, is involved in a variety of processes, such as gene silencing in position effect variegation (PEV), the control of gypsy insulator sequences, regulation of homeotic gene expression, and programmed cell death. We have isolated a large number of mod(mdg4) cDNAs, representing 21 different isoforms generated by alternative splicing. The deduced proteins are characterized by a common N terminus of 402 amino acids, including the BTB/POZ-domain. Most of the variable C termini contain a new consensus sequence, including four positioned hydrophobic amino acids and a Cys(2)His(2) motif. Using specific antibodies for two protein isoforms, we demonstrate different distributions of the corresponding proteins on polytene chromosomes. Mutations in the genomic region encoding exons 1-4 show enhancement of PEV and homeotic transformation and affect viability and fertility. Homeotic and PEV phenotypes are enhanced by mutations in other trx-group genes. A transgene containing the common 5' region of mod(mdg4) that is present in all splice variants known so far partially rescues the recessive lethality of mod(mdg4) mutant alleles. Our data provide evidence that the molecular and genetic complexity of mod(mdg4) is caused by a large set of individual protein isoforms with specific functions in regulating the chromatin structure of different sets of genes throughout development.


Assuntos
Processamento Alternativo , Sequência Consenso , Proteínas de Drosophila , Drosophila/genética , Fatores de Transcrição/genética , Sequência de Aminoácidos , Animais , Sequência de Bases , Mapeamento Cromossômico , DNA Complementar , Proteínas de Ligação a DNA/genética , Drosophila/embriologia , Drosophila/metabolismo , Larva , Dados de Sequência Molecular , Mutagênese , Oogênese , Fenótipo , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Pupa , Fatores de Transcrição/metabolismo , Transformação Genética
20.
Nuklearmedizin ; 38(4): 95-100, 1999.
Artigo em Alemão | MEDLINE | ID: mdl-10392373

RESUMO

AIM: The purpose of this work was to prove the clinical significance of nuclear medical procedures in pre- and intraoperative detection of the SLN. METHODS: In the past 4 years, we did preoperative lymphoscintigraphy in 214 patients (pts.). Intraoperative localisation of the SLN with a hand-held gamma probe followed in 150 pts. RESULTS: In 214 pts. 247 lymphatic draining regions were found by preoperative scintigraphy. In 3 pts. with melanoma of the cheek no lymphatics/lymph nodes could be detected. 14 pts. showed interval lymph nodes. In 150 pts. gamma probe guided SLNE was done. In 2 pts. with supraclavicular primary tumor 4 SLN had been defined by preoperative scintigraphy but only 2 could be found intraoperatively. In all other cases (98.7%) the sentinel node was detected correctly by the gamma probe and then removed. In 19 of 150 pts. (12.7%) metastases were detected in the pathologic specimen. The incidence of lymph node metastases showed a continuous increase from 0% at tumor stage pT1 to 44% at stage pT4. CONCLUSION: SLNE is an accurate method to determine nodal involvement in melanoma and minimizes operative invasiveness in melanoma surgery.


Assuntos
Metástase Linfática/diagnóstico por imagem , Melanoma/diagnóstico por imagem , Melanoma/cirurgia , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Câmaras gama , Humanos , Excisão de Linfonodo , Masculino , Pessoa de Meia-Idade , Monitorização Intraoperatória , Cintilografia
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