RESUMO
The generation of low emittance electron beams from laser-driven wakefields is crucial for the development of compact x-ray sources. Here, we show new results for the injection and acceleration of quasimonoenergetic electron beams in low amplitude wakefields experimentally and using simulations. This is achieved by using two laser pulses decoupling the wakefield generation from the electron trapping via ionization injection. The injection duration, which affects the beam charge and energy spread, is found to be tunable by adjusting the relative pulse delay. By changing the polarization of the injector pulse, reducing the ionization volume, the electron spectra of the accelerated electron bunches are improved.
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OBJECTIVES: To investigate the relationship between total uterine artery blood volume flow rate (TVFR) and birth weight and gestational age at delivery, and to establish normal ranges of TVFR throughout pregnancy. METHODS: This was a prospective cohort study of 334 nulliparous women booking antenatal care at University College London Hospital between August 2008 and September 2009. Women underwent a transabdominal ultrasound examination of uterine arteries for measurement of TVFR at 12, 20 and 24 weeks' gestation. Pregnancy outcomes were recorded and linear regression was used to study the relationship between TVFR and gestational age at delivery and birth weight. RESULTS: A total of 551 ultrasound scans were performed. There was a significant, positive correlation between TVFR at 11-13 weeks (TVFR1) and at 22-26 weeks (TVFR3) and birth weight. For every 100-mL/min increase in TVFR1 and TVFR3, there was an increase in birth weight of 45 g and 27 g, respectively. There was also a positive association between TVFR1 and gestational age at delivery, with a 1.4-day increase in gestational age for every 100-mL/min increase of TVFR1. CONCLUSION: Ultrasound measurement of TVFR in the first trimester is significantly associated with both birth weight and gestational age at delivery. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
Assuntos
Ultrassonografia Pré-Natal/métodos , Artéria Uterina/diagnóstico por imagem , Peso ao Nascer , Volume Sanguíneo , Feminino , Idade Gestacional , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Estudos ProspectivosRESUMO
OBJECTIVE: To evaluate the clinical accuracy of the IONA® test for aneuploidy screening. METHODS: This was a multicenter blinded study in which plasma samples from pregnant women at increased risk of trisomy 21 underwent cell-free DNA analysis utilizing the IONA test. For each sample, the IONA software generated a likelihood ratio and a maternal age-adjusted probability risk score for trisomies 21, 18 and 13. All results from the IONA test were compared against accepted diagnostic karyotyping. RESULTS: A total of 442 maternal samples were obtained, of which 437 had test results available for analysis and assessment of clinical accuracy. The IONA test had a detection rate of 100% for trisomies 21 (n = 43; 95% CI, 87.98-100%), 18 (n = 10; 95% CI, 58.72-100%) and 13 (n = 5; 95% CI, 35.88-100%) with cut-offs applied to likelihood ratio (cut-off > 1 considered high risk for trisomy) and probability risk score incorporating adjustment for maternal age (cut-off ≥ 1/150 considered high risk for trisomy). The false-positive rate (FPR) was 0% for trisomies 18 and 13 with both analysis outputs. For trisomy 21, a FPR of 0.3% was observed for the likelihood ratio, but became 0% with adjustment for maternal age. CONCLUSION: This study indicates that the IONA test is suitable for trisomy screening in a high-risk screening population. The result-interpretation feature of the IONA software should facilitate wider implementation, particularly in local laboratories, and should be a useful addition to the current screening methods for trisomies 21, 18 and 13.
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Transtornos Cromossômicos/diagnóstico , Síndrome de Down/diagnóstico , Testes Genéticos/métodos , Testes para Triagem do Soro Materno/métodos , Trissomia/diagnóstico , Adolescente , Adulto , Transtornos Cromossômicos/embriologia , Transtornos Cromossômicos/genética , Cromossomos Humanos Par 13/genética , Cromossomos Humanos Par 18/genética , Síndrome de Down/embriologia , Síndrome de Down/genética , Feminino , Idade Gestacional , Humanos , Cariotipagem , Idade Materna , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Gravidez , Primeiro Trimestre da Gravidez/sangue , Gravidez de Alto Risco/sangue , Gravidez de Alto Risco/genética , Método Simples-Cego , Trissomia/genética , Síndrome da Trissomia do Cromossomo 13 , Síndrome da Trissomía do Cromossomo 18 , Adulto JovemRESUMO
Caesarean section in the second stage of labour is a difficult procedure, with little published evidence to guide practice. We investigated the background and morbidity. Case notes of all emergency caesareans at full dilatation over 1 year in two hospitals were studied for demographics, grade of attending doctor, other methods of surgical delivery and morbidity. A total of 91 (15.3%) of 595 emergency caesareans were performed at full dilatation. Instrumental delivery was attempted in 36 (40%). A consultant was present in 29 (32%). In 16 (18%), the venous pH was Assuntos
Segunda Fase do Trabalho de Parto
, Adulto
, Serviços Médicos de Emergência
, Feminino
, Hospitais Gerais
, Humanos
, Complicações do Trabalho de Parto/epidemiologia
, Gravidez
, Resultado da Gravidez
, Estudos Retrospectivos
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High order multiple pregnancies have substantial morbidity and mortality. Fertility treatment is commonly responsible for their conception and is available globally with variable regulation. We investigated cross-border fertility treatment in these pregnancies in a UK fetal medicine unit, recording mode of conception, country of fertility treatment, reason for non-UK treatment and fetal reduction. Over an 11-year period, 109 women had a high order multiple pregnancy. Ninety-four women (86%) conceived with fertility treatment of whom 24 (26%) had this performed overseas. Cross-border fertility treatment poses an increasing challenge to obstetricians. National data on its occurrence is urgently needed.
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Infertilidade/terapia , Serviços de Saúde Materna/estatística & dados numéricos , Gravidez Múltipla/estatística & dados numéricos , Técnicas de Reprodução Assistida/estatística & dados numéricos , África , Ásia , Europa (Continente) , Feminino , Humanos , Londres/epidemiologia , Gravidez , Estudos Retrospectivos , Medicina Estatal , Reino Unido , Estados UnidosRESUMO
Surgical resection of the esophagus remains the mainstay of treatment for esophageal cancer. However, esophagectomy is associated with significant morbidity and mortality in the postoperative period. We have recently altered our practice pattern to include minimally invasive esophagectomy (MIE) as the approach of choice in the hope of minimizing morbidity associated with this procedure. In this retrospective analysis, we compare outcomes of our first year performing MIE to the previous 3 years of open esophagectomy (OE) at a single teaching hospital. Sixty-five patients underwent esophagectomy between June 2002 and July 2006. Among these, 22 patients underwent MIE between June 2005 and July 2006 and 43 patients underwent OE. The two groups were comparable with regards to age, comorbidities and pathologic stage. The MIE group had less operative blood loss (178 mL vs. 356 mL), decreased respiratory complications requiring mechanical ventila-tion (5% vs. 23%), increased number of lymph nodes procured per procedure (15 vs. 8), and increased number of patients discharged within 10 days (72% vs. 28%) when compared to the OE group. No difference was identified in mortality, complications, or length of stay.
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Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitais de Ensino , Humanos , Masculino , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Minimamente Invasivos , Estudos RetrospectivosRESUMO
The Orion high-resolution x-ray (OHREX) spectrometer has been a successful tool for measuring the shapes of density-broadened spectral lines produced in short-pulse heated plasmas at the Orion laser facility. We have recently outfitted the instrument with a charge-couple device (CCD) camera, which greatly increased the accuracy with which we can perform line-shift measurements. Because OHREX is located on the outside of the Orion target chamber, no provisions for the shielding of electromagnetic pulses are required. With the CCD, we obtained a higher signal-to-noise ratio than we previously obtained with an image-plate detector. This allowed us to observe structure in the image produced by the diffraction from the two OHREX crystals, which was highly reproducible from shot to shot. This structure will ultimately limit the accuracy of our spectroscopic measurements.
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BACKGROUND: Minimally invasive esophagectomy is a complex surgical procedure. We recently began performing thoracic mobilization of the esophagus with the patient in the prone position, not the left lateral decubitus position, in the hope of minimizing the number of technical challenges. METHODS: Six consecutive minimally invasive esophagectomies were performed using prone thoracoscopic esophageal mobilization with creation of cervical anastamosis. Our esophagectomy database was evaluated for outcomes, including operative time, estimated blood loss, complications, and length of hospital stay. RESULTS: We were successful in our first six attempts, with a mean blood loss of 61 cc. Mean operative time for thoracoscopy was 80 min. Operative times were steady over the first six prone cases at 105, 85, 70, 55, 80, and 85 min. Three of the six patients had no complications. Median postoperative length of hospital stay was 11.5 days, and there were no deaths. CONCLUSIONS: This technical report and case series demonstrates that prone thoracoscopic esophageal mobilization appears to be a reasonable alternative to the same procedure performed with the patient in the decubitus position. We find the technique to simplify portions of an otherwise difficult surgical procedure. Further evaluation with larger number of patients should be performed.
Assuntos
Esofagectomia/métodos , Toracoscopia/métodos , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Decúbito VentralRESUMO
OBJECTIVE: Esophagectomy may lead to impairment in gastric emptying, unless a pyloroplasty or pyloromyotomy is performed. These procedures may be technically challenging during minimally invasive esophagectomy, and they are associated with a small but definable morbidity, such as leakage and dumping syndrome. We sought to determine the results of our early experience with injecting the pylorus with botulinum toxin instead of conventional pyloric drainage. METHODS: Fifteen patients who had undergone esophagectomy and injection of the pylorus with botulinum toxin were identified. Twelve patients had undergone botulinum toxin injection at the time of minimally invasive esophagectomy, and the remaining three had been treated endoscopically after surgery. The latter three patients had undergone esophagectomy with either no pyloric drainage (n = 2) or an inadequate pyloromyotomy (n = 1), and they presented in the postoperative period with delayed gastric emptying. The adequacy of emptying after injection was assessed by the patients' ability to tolerate a regular diet, a barium swallow, and a nuclear gastric emptying study. RESULTS: No patient injected with botulinum toxin during esophagectomy developed delayed gastric emptying or aspiration pneumonia in the perioperative period. Eight of these patients underwent a nuclear emptying scan at a median of 4.2 months after surgery, which showed a mean emptying half-life of 100 min. With a median follow-up of 5.3 months, one patient (8%) required reintervention for symptoms of gastric stasis, presumably after the effect of the toxin subsided. All three patients injected postoperatively demonstrated an improvement in symptoms of gastric outlet obstruction and were able to resume a regular diet. CONCLUSIONS: Injection of the pylorus with botulinum toxin can be performed safely in patients undergoing esophagectomy. Longer-term studies are needed to clarify the efficacy and durability of this technique compared to the accepted procedures of pyloromyotomy or pyloroplasty.
Assuntos
Toxinas Botulínicas/administração & dosagem , Esofagectomia/efeitos adversos , Esvaziamento Gástrico/efeitos dos fármacos , Obstrução da Saída Gástrica/tratamento farmacológico , Obstrução da Saída Gástrica/prevenção & controle , Toxinas Botulínicas/uso terapêutico , Esquema de Medicação , Endoscopia , Obstrução da Saída Gástrica/etiologia , Humanos , Injeções/métodos , Cuidados Intraoperatórios , Procedimentos Cirúrgicos Minimamente Invasivos/efeitos adversos , Projetos Piloto , Cuidados Pós-Operatórios , Piloro/efeitos dos fármacos , Estudos Retrospectivos , Fatores de TempoRESUMO
Thermal conductivity is one of the most crucial physical properties of matter when it comes to understanding heat transport, hydrodynamic evolution, and energy balance in systems ranging from astrophysical objects to fusion plasmas. In the warm dense matter regime, experimental data are very scarce so that many theoretical models remain untested. Here we present the first thermal conductivity measurements of aluminum at 0.5-2.7 g/cc and 2-10 eV, using a recently developed platform of differential heating. A temperature gradient is induced in a Au/Al dual-layer target by proton heating, and subsequent heat flow from the hotter Au to the Al rear surface is detected by two simultaneous time-resolved diagnostics. A systematic data set allows for constraining both thermal conductivity and equation-of-state models. Simulations using Purgatorio model or Sesame S27314 for Al thermal conductivity and LEOS for Au/Al release equation-of-state show good agreement with data after 15 ps. Discrepancy still exists at early time 0-15 ps, likely due to non-equilibrium conditions.
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Fluorescence and flow microfluorometric methods have been established for the detection and evaluation of IgE-bearing human leukocytes in various cell preparations including those where basophils are present at low percentages. Quantitative techniques for the determination of basophil purity, viability, and cell surface antigens including IgE are described. Use of these methods will facilitate the identification and phenotypic analysis of human IgE-bearing cells in a wide variety of biological fluids.
Assuntos
Basófilos/imunologia , Imunoglobulina E/análise , Antígenos CD/análise , Antígenos de Superfície/análise , Separação Celular/métodos , Sobrevivência Celular , Citometria de Fluxo , Antígenos HLA-DR/análise , HumanosRESUMO
BACKGROUND: The insertion and subsequent removal of chest tubes are frequently performed procedures. We hypothesize that routine chest radiographs obtained after chest tube removal to confirm the absence of any post-procedure complications have little impact on clinical management. MATERIALS AND METHODS: A 5-year retrospective study of 73 patients with tube thoracotomies was performed in a level II trauma center's intensive care unit. Patients were identified from billing records for chest tube placement. Medical records and official chest x-ray film reports, both before and after removal, were reviewed, and demographic data were collected. RESULTS: Of the 73 patients examined, only 8 had postprocedure reports that differed from the preprocedure reports. Two of these 8 patients required reinsertion of a chest tube to treat the recurrence of a significant pneumothorax. However, the decision to reinsert the chest tube was based on the patient's clinical appearance rather than on the x-ray findings. CONCLUSION: Chest radiography following the removal of chest tubes should not be a routinely performed procedure, but should preferably be based on the good clinical judgement and discrimination of the surgeon.
Assuntos
Tubos Torácicos , Radiografia Torácica/estatística & dados numéricos , Controle de Custos , Custos e Análise de Custo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia Torácica/economia , Estudos Retrospectivos , Toracostomia , Centros de TraumatologiaRESUMO
OBJECTIVE: There is an increasing number of elderly patients presenting with potentially-resectable lung malignancy. The objective of this study is to evaluate the modern perioperative morbidity and mortality in patients undergoing oncologic lung resection and to analyse the trend over a 26-year period in our experience. METHODS: Between 1971 and 1996, 1506 patients underwent lung resection for malignancy. We reviewed the 30-day perioperative risk in a group of 385 (25.6%) patients aged 70 years and older operated on for intended cure of lung malignancy. Operations included 293 (77%) lobectomies, 24 pneumonectomies (6%), 16 bilobectomies (4%) and 52 wedge or segmental resections (13%). The pathology was bronchogenic carcinoma in 89% and metastasis or other tumours in 11% of patients. We compared the 30-day perioperative risk between the elderly group (age 70 or greater) and a cohort of 180 patients (control) 69 years and younger. RESULTS: The mortality for all resections in elderly group was 4.2% (16/385) and was 1.6% for the control group. Mortality in the octogenarian group was 2.8%. Female gender correlated with a decreased risk of death, with only two of 16 deaths in females (P < 0.005). Overall morbidity was higher in the study than in control patients (34% vs. 25%, n.s.), although major morbidity was similar in both groups (13.2% vs. 13%). Abnormal pulmonary-function testing and positive cardiac history did not correlate with increase overall or specific risk. Pneumonectomy carried a higher risk for death, with three of 24 deceased (12.5%; P < 0.05). Changes in outcome were analysed over two time periods: the mortality in the early period (1971-1982), 11.1% (8/72), was significantly elevated above the control group, while mortality in the modern period (1983-1994) was not, with a rate of 2.6% (8/313). CONCLUSIONS: In our series, mortality associated with operative treatment for lung malignancy in the elderly declined, so age alone no longer appears to be a risk factor. Age remains a risk factor for overall, but not major, morbidity. Pneumonectomy should undertaken cautiously in this age group. Based on this data, functional elderly patients should not be denied curative lung resection based on age alone.
Assuntos
Neoplasias Pulmonares/cirurgia , Pneumonectomia , Adenocarcinoma/cirurgia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Carcinoma Broncogênico/mortalidade , Carcinoma Broncogênico/cirurgia , Carcinoma de Células Escamosas/cirurgia , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pneumonectomia/mortalidade , Estudos Retrospectivos , Fatores de Risco , Análise de SobrevidaRESUMO
During late 1998 and early 1999, planning officers in Cornwall predicted a huge increase in summer visitors to the county to observe the August solar eclipse. There was the possibility that a mass gathering in Cornwall could overload existing arrangements for handling accident and emergency patients. We therefore set up a telemedicine system to support the county's minor injury units (MIUs) from hospitals throughout the UK. Six main hospital accident and emergency departments outside Cornwall with existing links to their own MIUs were twinned with 10 of the 11 MIUs in Cornwall before the expected date of the gathering. The network was live for nine days, starting four days before the eclipse, and 2045 patients were seen in the 10 MIUs. There were 93 telemedicine calls from the 10 MIUs, involving 91 patients. Overall, 4.6% of the patients required a telemedicine consultation. Fifty-seven calls were made during working hours. Thirty-four patients were referred for further management, of whom 18 were referred on the same day. The transfer of telemedical support to a national network was successful.
Assuntos
Serviços Médicos de Emergência/organização & administração , Administração dos Cuidados ao Paciente/normas , Atividade Solar , Telemedicina/organização & administração , Inglaterra , Feminino , Humanos , Masculino , Administração dos Cuidados ao Paciente/métodos , Administração dos Cuidados ao Paciente/organização & administração , Ferimentos e Lesões/epidemiologiaRESUMO
Improving the design and performance of medical stents for implantation in the human body is of current interest. This paper describes a study of fatigue-crack propagation behavior in the superelastic alloy Nitinol. Specifically, the objective of this work was to study the effect of environment on cyclic crack-growth resistance in an approximately 50Ni-50Ti (atom %) alloy and to provide the necessary data for the safe life prediction of Nitinol endovascular stents. The material selected for this study was heat treated such that it was superelastic at human body temperature; this was confirmed with monotonic uniaxial tensile tests. Characterization of fatigue-crack growth rates was performed at 37 degrees C on disk-shaped compact-tension samples in environments of air, aerated deionized water, and aerated Hank's solution (a simulated body fluid). The effect of cyclic loading on the uniaxial constitutive behavior was investigated at a strain range of 6.4%, and results indicate that the magnitude of available superelastic strain ( approximately 5.0%) is maintained even after cyclic softening. However, despite the persistence of nucleating the stress-induced martensitic phase after cycling with a maximum strain slightly below the plastic yield point, Nitinol was found to have the lowest fatigue-crack growth resistance of the principal metallic alloys currently used for implant applications.
Assuntos
Ligas/química , Prótese Vascular , Stents , Líquidos Corporais , Elasticidade , Humanos , Soluções Isotônicas , Estresse MecânicoRESUMO
By means of a serial horizontal microscopic sections and a special computer, three-dimensional reconstruction of seven superficial multicentric basal cell carcinomas was carried out. All foci of tumor were observed to be interconnected, which suggests a unicentric origin for this subtype of basal cell carcinoma.
Assuntos
Carcinoma Basocelular/patologia , Neoplasias Cutâneas/patologia , Histocitoquímica , Humanos , Processamento de Imagem Assistida por ComputadorRESUMO
Gastrointestinal (GI) fistulas allow abnormal diversions of GI contents, digestive juices, water, electrolytes, and nutrients from one hollow viscus to another or to the skin, potentially precipitating a wide variety of pathophysiologic effects. Mortality rates have decreased significantly during the past few decades from as high as 40% to 65% to 5.3% to 21.3% largely as a result of advances in intensive care, nutritional support, antimicrobial therapy, wound care, and operative techniques. The primary causes of death secondary to enterocutaneous fistulas have been, and continue to be, malnutrition, electrolyte imbalances, and sepsis, especially in high-output fistulas, which continue to have a mortality rate of about 35%. Priorities in the management of GI fistulas include restoration of blood volume and correction of fluid, electrolyte, and acid-base imbalances; control of infection and sepsis with appropriate antibiotics and drainage of abscesses; initiation of GI tract rest including secretory inhibition and nasogastric suction; control and collection of fistula drainage with protection of the surrounding skin; and provision of optimal nutrition by total parenteral nutrition (TPN) or enteral nutrition (EN) (or both). The role of nutrition support in the management of enterocutaneous fistulas as either TPN or EN is primarily one of supportive care to prevent malnutrition, thereby obviating further deterioration of an already debilitated patient. It has been shown in several studies that TPN has substantially improved the prognosis of GI fistula patients by increasing the rate of spontaneous closure and improving the nutritional status of patients requiring repeat operations. Moreover, other studies have shown that nutritional support decreases or modifies the composition of the GI tract secretions and is thus considered to have a primary therapeutic role in the management of fistula patients. Finally, if a fistula has not closed within 30 to 40 days, or if it is unlikely to close because of a variety of collateral or compounding pathophysiologic conditions, consideration must be given to operative resection of the fistula while continuing to maintain the previous nutritional and metabolic support. The morbidity and mortality rates in such unfortunate patients remain high despite the many recent advances in surgical and metabolic technology.
Assuntos
Fístula Gástrica/terapia , Fístula Intestinal/terapia , Apoio Nutricional , Antibacterianos/uso terapêutico , Volume Sanguíneo , Cuidados Críticos , Fístula Cutânea/fisiopatologia , Nutrição Enteral , Fístula Gástrica/complicações , Fístula Gástrica/fisiopatologia , Conteúdo Gastrointestinal , Humanos , Fístula Intestinal/complicações , Fístula Intestinal/fisiopatologia , Secreções Intestinais , Distúrbios Nutricionais/etiologia , Distúrbios Nutricionais/terapia , Nutrição Parenteral Total , Prognóstico , Reoperação , Sepse/etiologia , Sepse/terapia , Procedimentos Cirúrgicos Operatórios , Taxa de Sobrevida , Desequilíbrio Hidroeletrolítico/etiologia , Desequilíbrio Hidroeletrolítico/terapiaRESUMO
Dopamine (DA) modulates renal tubular sodium transport by actions at both brush border (BBM) and basolateral membranes (BLM). DA receptors have been demonstrated in proximal tubule but the subtype of DA receptor in either BBM or BLM has not been determined. DA-1 receptors were quantitated by the specific binding of 125I-SCH 23982, a DA-1 antagonist (defined by 20 microM SCH 23390, a DA-1 antagonist) and DA-2 receptors by the specific binding of 3H-methyl-spiroperidol or 3H-spiroperidol (defined by 30 microM trifluperidol, a predominantly DA-2 antagonist). The specific binding of 125I-SCH 23982 and 3H-methyl-spiroperidol or 3H-spiroperidol were saturable with time and ligand concentration and reversible. Analysis of Rosenthal plots by non-linear regression revealed a high affinity site and a very low affinity site for both BLM and BBM. Maximum receptor density was similar in BBM and BLM. Competition experiments with 125I-SCH 23982 revealed high and low affinity binding sites in both BBM and BLM. The high affinity site was characteristic of a DA-1 receptor. Competition experiments with 3H-spiroperidol were also suggestive of DA-2 receptors. DA-1 but not DA-2 drugs increased adenylate cyclase and phospholipase-C activities in both BBM and BLM. However, their effects were greater in BLM than BBM. We conclude that DA-1 and DA-2 receptors are present in both BBM and BLM in canine kidney. Renal DA-1 receptors are linked to stimulation of both adenylate cyclase and phospholipase-C activity.
Assuntos
Benzazepinas , Benzazepinas/análogos & derivados , Córtex Renal/metabolismo , Microvilosidades/metabolismo , Receptores Dopaminérgicos/metabolismo , Adenilil Ciclases/metabolismo , Animais , Benzazepinas/metabolismo , Ligação Competitiva , Membrana Celular/metabolismo , Cães , Antagonistas de Dopamina , Radioisótopos do Iodo , Cinética , Receptores de Dopamina D1 , Receptores de Dopamina D2 , Espiperona/metabolismo , Fosfolipases Tipo C/metabolismoRESUMO
We have previously reported that in sensory neurons of mice harboring latent herpes simplex virus (HSV), a novel virus-encoded RNA species termed the latency-associated transcript (LAT) is abundant. To investigate a potential function for LAT in the latent state, we have engineered a deletion in HSV-1 strain KOS(M) which abolishes LAT expression. The deletion virus (KOS 8117) is not altered for virulence or the ability to replicate in mouse cells in vivo or in vitro. Although no transcripts were detected in lumbosacral ganglia of mice after virus inoculation on scarified rear footpads, the deletion virus established a latent infection since infectious virus could be recovered by explanting and cultivating ganglia in vitro with permissive cells. These results indicate that expression of LAT is not an absolute requirement for the establishment or maintenance of the latent state or for recovery of infectious virus from the latent state by in vitro co-cultivation. Since no viral-encoded transcripts were detected in cells latently infected with KOS 8117, maintenance of the latent infection also appears to be exclusively a neuronal function.
Assuntos
RNA Viral/genética , Simplexvirus/crescimento & desenvolvimento , Ativação Viral/genética , Animais , Autorradiografia , Análise Mutacional de DNA , Gânglios Espinais/citologia , Gânglios Espinais/microbiologia , Masculino , Camundongos , Hibridização de Ácido Nucleico , Simplexvirus/genética , Transcrição Gênica , Cultura de Vírus , Replicação ViralRESUMO
The renal vasodilatory response to beta-2 adrenoceptor stimulation is greater in fetal than adult sheep. Since this phenomenon could not be explained by differences in cAMP-mediated events, we examined the ontogeny of renal beta adrenoceptor subtypes by radioligand binding using the beta adrenergic antagonist 125I-pindolol. The specific binding of 125I-pindolol was saturable, reversible, and stereoselective. Competition studies using the selective beta-1 and beta-2 adrenergic antagonists (ICI 89406 and ICI 118551, respectively) revealed two beta adrenoceptor subtypes in adult kidneys but only the beta-2 subtype in fetal kidneys. Preincubation of renal cortical membranes with either the beta-1 or the beta-2 adrenergic antagonist prior to competition studies in adult kidneys decreased specific binding and resulted in the detection of only one beta adrenoceptor subtype. Preincubation of fetal kidneys with the beta-1 adrenergic antagonist did not affect binding characteristics; preincubation of fetal kidneys with the beta-2 adrenergic antagonist markedly decreased specific binding from 64 +/- 2% (n = 4) to 29 +/- 2% (n = 3) (P less than 0.05). Analysis of Rosenthal plots revealed similar beta adrenoceptor densities and affinities between fetal and adult kidneys.(ABSTRACT TRUNCATED AT 250 WORDS)