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11.
12.
Brian D Perkins Claire S Nicholas Lisa M Baye Brian A Link John E Dowling 《Developmental dynamics》2005,233(2):680-694
Several molecules, such as growth factors and neurotrophic factors, are required both for the differentiation of specific retinal cell types and the long-term cell survival of all retinal neurons. As diffusible factors, these molecules act non-cell-autonomously. Here, we describe the loss of function phenotype for dazed (dzd), a gene that acts cell-autonomously for retinal cell survival and affects the differentiation of rod photoreceptors and the Muller glia. By 3 days after fertilization, dazed mutant embryos have small eyes and slight heart edema. Acridine orange staining indicated a significant degree of retinal cell death occurring by 48 hr after fertilization, and histological analysis revealed that dying cells were found in the inner and outer nuclear layers and near the marginal zones. Although molecular and morphological differentiation of the inner retina and cone photoreceptors occurred, rod photoreceptors failed to differentiate beyond a small patch in the ventral retina and rod precursors failed to respond to exogenously added retinoic acid, which normally potentiated rod differentiation. Mosaic analysis indicated that the dazed gene acts cell-autonomously for rod production and cell survival, as dazed clones failed to produce rods outside the ventral patch and dazed cells were not maintained in wild-type hosts. Raising mutants under constant light resulted in severe retinal degeneration, whereas raising embryos under constant darkness did not provide any additional protection from cell death. Behavioral analysis showed that a subpopulation of adult fish that were heterozygous for the dazed mutation had elevated visual thresholds and were night blind, suggesting that dazed may also be required for long-term dim-light vision. Taken together, our studies suggest a role for the dazed gene in rod and Muller cell development and overall retinal cell survival and maintenance. 相似文献
13.
What are often called "little-ticket" items--X-rays and laboratory tests--account for 25-30% of all health care costs. Two such items were the focus of this study, which took place at an inner-city community health center operated by the Department of Family Medicine of Cook County Hospital and involved 20 family practice residents over a period of nine weeks. The first item was the complete blood count (CBC) with differential, a prototype of a low-cost, high-volume test often ordered by reflex; the second, the thyroid stimulating hormone (TSH) test, a high-cost, low-volume test normally associated with a differential diagnosis or clinical reasoning. Through the use of a simple educational intervention based on quality of care, not cost-containment, and an audit feedback system, the authors were able to reduce significantly the rates of ordering TSH tests (p less than .0001) and CBCs (p = .05). This effect on the rates persisted five months after the intervention terminated. In addition, the percentage of TSH tests clinically indicated by explicit criteria increased significantly (p less than .001) during the intervention. However, this effect showed signs of diminishing five months after the intervention ended. The percentage of CBCs clinically indicated did not change significantly as a result of this intervention. 相似文献
14.
Role of the alveolar macrophage in host defense and immunity to Legionella micdadei pneumonia in the guinea pig 总被引:8,自引:0,他引:8
Guinea pigs develop a lethal pneumonia after intratracheal infection with Legionella micdadei, and the lung displays pathological changes similar to those observed in humans. To investigate the role of the resident alveolar macrophage in the pathogenesis of L. micdadei pneumonia, guinea pig alveolar macrophages obtained by bronchoalveolar lavage were cultured in vitro and infected with L. micdadei. In the absence of opsonins L. micdadei was phagocytized by, and multiplied within, alveolar macrophages with greater than a 100-fold increase in cell-associated colony forming units over 20 h. L. micdadei opsonized with complement or antibody multiplied within alveolar macrophages at the same rate as unopsonized bacteria. Guinea pigs which were treated with antimicrobials after infection with L. micdadei and recovered from the pneumonia were immune to challenge with an otherwise lethal inoculum of L. micdadei. However, the growth curve of both unopsonized and opsonized L. micdadei in the alveolar macrophages from immune animals was essentially identical to that in macrophages from susceptible animals. Thus, the resident alveolar macrophage is not capable of limiting the growth of Legionella. Rather, the alveolar macrophages appear to be the primary site of Legionella multiplication within the lung. Although alveolar macrophages may participate in other aspects of pulmonary immunity to the legionellae, these data indicate that the alveolar macrophage alone does not act as an effector cell in cell-mediated immunity to Legionella. 相似文献
15.
A foot-pad oedema model was used to investigate the presence of free radicals using a chemiluminescence method. This model is an example of a cell mediated hypersensitivity reaction. Male rats were inoculated in the scruff with Freund's Complete Adjuvant (FCA) on Day 0 and then challenged 6 days later with FCA in one hind paw. An acute inflammatory reaction was initiated over the following 96 hours and within 4 hours of induction, reactive oxygen species were detected in the inflamed tissue. A peak of chemiluminescence activity was seen 8 hours after the induction of the inflammatory reaction, well before maximum oedema was observed. Using mannitol, catalase and DABCO to elucidate the nature of the reactive oxygen species it was found that hydroxyl radicals, hydrogen peroxide and singlet oxygen all contributed to this burst of oxidative activity and are therefore probably involved with the process of lipid peroxidation and the severity of an inflammatory reaction. 相似文献
16.
Chenodeoxycholic acid treatment of gallstones. A follow-up report and analysis of factors influencing response to therapy. 总被引:4,自引:0,他引:4
We treated 70 patients with gallstones with chenodeoxycholic acid over 3 1/2 years and analyzed the factors influencing the outcome of therapy. This treatment was unsuccessful in 11 patients with radiopaque gallstones and in seven with nonfunctioning gallbladders, but 64 per cent with radiolucent gallstones treated for six months or more showed partial or complete gallstone dissolution, and of those whose bile became unsaturated with cholesterol, 100 per cent had evidence of dissolution. In patients with partial or complete gallstone dissolution, the mean post-treatment biliary cholesterol saturation index--0.78 +/- 0.04 (S.E.M.)--was significantly less (P less than 0.001), and the dose of chenodeoxycholic acid (14.4 +/- 1.0 mg per kilogram of body weight per day) significantly more (P less than 0.025) than in those whose gallstones did not change (1.15 +/- 0.04 and 10.6 +/- 1.2 respectively). In patients with radiolucent gallstones, the dose of chenodeoxycholic acid should be based on body weight; 14 to 15 mg per kilogram of body weight per day effectively lowers the saturation index and dissolves gallstones. 相似文献
17.
The transplanted kidney as a source of cytomegalovirus infection. 总被引:25,自引:0,他引:25
M Ho S Suwansirikul J N Dowling L A Youngblood J A Armstrong 《The New England journal of medicine》1975,293(22):1109-1112
To determine the incidence of cytomegalovirus infection in renal-transplant recipients we followed 32 prospectively for six months after operation. As judged by serologic change and virus isolation the infection rate for the entire group was 66 per cent (21 of 32 patients) - 59 per cent (13 of 22) for seronegative patients and 80 per cent (eight of 10) for seropositive patients. Of 10 seronegative patients who received kidneys from seronegative donors, only three became infected. However, of 12 seronegative patients who received kidneys from seropositive donors, 10 became infected. Thus, there was a significant correlation between development of infection and seropositivity of the donor (P = 0.03), particularly when the recipient was seronegative (P = 0.02). Five possible and four definite recognizable clinical illnesses were associated with cytomegalovirus infection; all except two were in initially seronegative subjects who received kidneys from seropositive donors. Primary infection and disease in nonimmune recipients may be caused by cytomegalovirus transmitted by the kidneys of latently infected seropositive donors. 相似文献
18.
Interaction of Angiotensin with Disseminated Intravascular Coagulation: A Possible Mechanism in the Genesis of Acute Renal Failure
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Alan N. Whitaker Ian Bunce Peter Nicoll Susanne V. Dowling 《The American journal of pathology》1973,72(1):1-12
Because of the importance of the renin-angiotensin system in renal homeostatic mechanisms, the effect of angiotensin administration upon disseminated intravascular coagulation has been studied in rabbits. An infusion of angiotensin II (0.1 μg/kg/min for 2 hours) produced neither histologic abnormalities in the kidneys nor an elevation of creatinine. After an infusion of thrombin (2.0 units/kg/min for 2 hours) only 3 of 10 rabbits, when sacrified 24 hours later, showed histologic lesions comprised of occasional fibrin thrombi and foci of tubular necrosis. Creatinine levels did not rise. In contrast, the combination of angiotensin and thrombin resulted in renal lesions in 12 of 14 animals. Four had frank cortical necrosis, while combinations of tubular necrosis, glomerular thrombosis and segmental glomerular infarction occurred in the others, together with elevated creatinine levels. Blockade of α-adrenoreceptors with phenoxybenzamine in 12 animals did not prevent either these histologic changes or creatinine elevation, showing that the effect of angiotensin was independent of α-adrenoreceptor stimulation. The synergistic interaction between angiotensin and disseminated intravascular coagulation was not explained by differences in the consumption of plasma fibrinogen but apparently was due to localization of fibrin thrombi within glomerular capillaries by the vasomotor actions of angiotensin, as has previously been shown to occur with α-adrenoreceptor simulation. Such a mechanism might contribute to renal glomerular deposition of fibrin in acute ischemic renal failure. 相似文献
19.
One-year prospective study of cases of suspected acute myocardial infarction managed by urban and rural general practitioners.
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A W Murphy D McCafferty J Dowling G Bury 《The British journal of general practice》1996,46(403):73-76
BACKGROUND: The role of the general practitioner in the management of patients with suspected acute myocardial infarction is important and specific. It has been recommended that eligible patients should receive thrombolysis within 90 minutes of alerting medical or ambulance services. The administration of prehospital thrombolysis by general practitioners is controversial. Most research into the management of acute myocardial infarction has been hospital based and has not explored differences between urban and rural general practice. AIM: In 1993-94 a one-year prospective survey was undertaken of samples of urban and rural general practitioners to examine their management of cases of suspected acute myocardial infarction and to determine whether differences in management existed between the two settings. METHOD: General practitioners were recruited through the continuing medical education faculty network of the Irish College of General Practitioners. Participating general practitioners completed a report form for cases of suspected acute myocardial infarction. Six-week follow-up forms were also completed. RESULTS: A total of 113 general practitioners (54 urban and 59 rural) participated in the study. A total of 57 general practitioners contributed 195 cases, 49 from urban and 146 from rural areas. The mean number of cases of suspected acute myocardial infarction per participant for urban and rural doctors was 0.9 and 2.5, respectively. Median delay time from onset of symptoms to contacting the general practitioner was 90 minutes for both urban and rural patients. Median general practitioner response times for urban and rural doctors were 10 and 15 minutes, respectively. Median estimated journey times from location of the patient to hospital for urban and rural patients were 10 and 40 minutes, respectively (P<0.001). Rural doctors were more likely, in comparison with their urban counterparts, to administer aspirin (given to 40% of patients versus 16%, P<0.01) but less likely to administer intravenous morphine (26% versus 41%, P<0.05). Twenty one patients (11%) died at the scene; follow-up forms were received for 94% of the remaining patients. Of these 163 patients, 99% were admitted to hospital; 49% were discharged with a diagnosis of acute myocardial infarction and a further 25% had final diagnoses consistent with acute coronary heart disease. CONCLUSION: This study suggests that the management of patients with suspected acute myocardial infarction differs in urban and rural settings. Delay times suggest that in order to meet current guidelines, prehospital thrombolysis must become a reality in rural areas. 相似文献
20.
Canny M Wright P Dowling J Murphy AW Bury G Duffy S McCarron F 《Irish medical journal》2000,93(9):278-279