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31.
MS Kurian RS de la Cuesta GL Waneck DT MacLaughlin TF Manganaro PK Donahoe 《Canadian Metallurgical Quarterly》1995,1(3):343-349
Müllerian inhibiting substance (MIS), an inhibitor of growth and development of the female reproductive ducts in male fetuses, requires precise proteolytic cleavage to yield its biologically active species. Human plasmin is now used to cleave and, thereby, activate immunoaffinity-purified recombinant human MIS at its monobasic arginine-serine site at residues 427-428. To avoid the need for exogenous enzymatic cleavage and to simplify purification, we created an arginine-arginine dibasic cleavage site (MIS RR) using site-directed mutagenesis to change the serine at position 428 (AGC) to an arginine (cGC). The mutant cDNA was then stably transfected into a MIS-responsive ocular melanoma cell line, OM431, followed by cloning for amplified expression to test its biological activity in vitro and in vivo. Media from each clone were assayed for production of MIS RR by a sensitive ELISA for holo-MIS, and high- and low-producing clones were selected for further study. Media from the highest MIS RR producer caused Müllerian duct regression in an organ culture bioassay. Other transfections were done with an empty vector (pcDNAI Neo) or a construct lacking the leader sequence and thus failing to secrete MIS, to serve as controls. The OM431 clones containing the MIS RR mutant were growth inhibited in monolayer culture. The high- and low-producing MIS RR OM431 clones, along with transfected OM431 controls, were injected into the tail veins of immunosuppressed severe combined immunodeficiency mice for in vivo analyses. Four to 6 weeks later, pulmonary metastases were counted in uniformly inflated lungs. OM431 clones containing the more easily cleaved MIS RR displayed a significant dose-dependent reduction in pulmonary metastases when compared to the lungs of animals given injections of OM431 clones containing empty vector, leaderless MIS, or wild-type MIS that requires activation by plasmin cleavage. Since the purification protocol of MIS RR is less complicated than that for wild-type MIS, which requires subsequent enzymatic activation, MIS RR can be used for scale-up production with increased yields for further therapeutic trials against MIS-sensitive tumors. 相似文献
32.
GW Lambert DM Kaye HS Cox M Vaz AG Turner GL Jennings MD Esler 《Canadian Metallurgical Quarterly》1995,57(3):255-267
Veno-arterial plasma concentration differences and regional organ plasma flows were used to quantify the relative amounts of 5-hydroxyindoleacetic acid (5-HIAA) contributed by various sites into the peripheral circulation. Positive venoarterial concentration gradients were found in the hepatosplanchnic, forearm, cardiac and jugular vessels in the healthy subjects. The renal circulation was determined to be the principal site of 5-HIAA clearance, extracting 18 +/- 2 nmol/min. The gut was the greatest contributor to the total 5-HIAA plasma pool with the relative contributions of the various organs being as follows: hepatosplanchnic organs 58%, skeletal muscle 26%, brain 6% and the heart 3%. The source of 5-HIAA stemming from these regional beds remains unknown, it may derive from serotonin taken up by and deaminated in ubiquitous endothelial cells, enterochromaffin cells of the gut, peripheral serotonergic nerves, serotonin turnover in platelets or perhaps the metabolism of serotonin taken up by sympathetic nerves. To test the latter hypothesis we examined 23 patients with chronic congestive heart failure and 9 patients with pure autonomic failure to investigate the possible effects of sympathetic nervous system overactivity and underactivity on peripheral 5-HIAA production and plasma 5-HIAA concentration. The resting arterial plasma 5-HIAA concentration in the heart failure patients was increased three-fold. This elevated plasma 5-HIAA concentration was attributable to an increased rate of whole body 5-HIAA production. The arterial 5-HIAA plasma concentration in the autonomic failure patients was paradoxically elevated, being 70% greater than that of the healthy subjects. The increased 5-HIAA plasma concentration in these patients was accounted for by a reduction in 5-HIAA plasma clearance. In all subjects studied there was a weak relationship only between total body norepinephrine spillover to plasma and the arterial 5-HIAA plasma concentration. We found that in healthy subjects the overflow of 5-HIAA into the hepatic vein was significantly related to the underlying degree of sympathetic activity. It can be concluded that 5-HIAA is produced at a number of sites throughout the body with the arterial plasma concentration being dependent on both the level of production and plasma clearance. By far the majority of 5-HIAA in plasma is derived from the gut with only minimal contribution from the brain. 相似文献
33.
MI Kostenetski? GT Gribinenko LS Kravtsova GL Ryzhova ZA Khripko 《Canadian Metallurgical Quarterly》1998,94(3):26-28
Central and cerebral hemodynamics was studied using echocardiography and transcranial dopplerography in 200 poststroke patients over 60 in the course of 5-year follow-up. It was established that cardiac hypodynamic syndrome, i.e. continuous or paroxysmal fall of minute blood volume below 3 l, is the most significant contributing factor in the onset of cerebral ischemia. Drugs are recommended for prevention of ischemic stroke. Those lowering cardiac hemodynamic reserve should be excluded in patients at high risk of acute failure of cerebral circulation. 相似文献
34.
Children with sickle-cell anaemia are predisposed to thrombotic strokes, the aetiology of which is unclear. We propose that erythropoietin, produced in response to chronic anaemia, is responsible for changes in platelet reactivity with a resulting increase in thromboses. This hypothesis is based on reports of enhanced aggregability of erythropoietin-driven platelets and an increased rate of thrombosis in patients receiving large doses of recombinant erythropoietin. Experiments in animals have shown that erythropoietin stimulates synthesis of platelets, that erythropoietin-driven platelets are hyper-reactive compared with age-matched control platelets, and that erythropoietin is pro-thrombotic. These data suggest that erythropoietin-dependent changes in platelet reactivity may potentiate thrombosis in sickle-cell anaemia, particularly in children who, compared with adults, have markedly higher erythropoietin concentrations and incidence of strokes. 相似文献
35.
"A Practice-Based Bioethic" is a regular column in Advanced Practice Nursing Quarterly. A practice-based approach is derived from, and therefore is intended to be appropriate to, the situation of a patient, the purpose of the health care setting, and the role of the nurse. It is based on a shared state of awareness, the foundation on which ethical interactions between nurse and patient occur. 相似文献
36.
F Gonzalez RL Walton B Shafer WE Matory GL Borah 《Canadian Metallurgical Quarterly》1993,91(7):1270-1276
The condition macromastia has not been defined and characterized precisely by the medical community. Whether the patient with hypertrophic breasts is a candidate for or can be helped by reduction mammaplasty is unclear to both the medical and the lay community. A prospective study of 39 women undergoing reduction mammaplasty surgery was initiated to answer these questions. Patients rated the severity of their somatic pain symptoms and discomfort before reduction mammaplasty and again after complete recovery. The severity of their symptoms and complaints was numerically graded and analyzed. These data were compared with similar data obtained from 40 "small-breasted" women of similar age. Headache, neck pain, back pain, shoulder pain, and bra strap groove pain were present in 60 to 92 percent of patients, and 97 percent of patients had at least three of these pain symptoms preoperatively. All the patients had reduction of their pain symptomatology postoperative, and 25 percent of the study patients had total elimination of pain symptoms by reduction mammaplasty. The postoperative incidence and severity of pain symptoms and discomfort complaints were statistically equivalent to or less than the levels in the control group. 相似文献
37.
Precise microphotometric assessment of intermediate cells from patients with normal cervical cytology and from patients with dysplasia or carcinoma in situ shows the existence of small but consistent differences. Marker features for the presence of premalignant and malignant disease can be extracted from the cell images of "normal"-appearing intermediate cells. The marker features and their diagnostic classification potential are described. 相似文献
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40.
Yi-Ou Li Tom Eichele Vince D. Calhoun Tulay Adali 《Journal of Signal Processing Systems》2012,68(1):31-48
In this work, we apply a novel statistical method, multiset canonical correlation analysis (M-CCA), to study a group of functional
magnetic resonance imaging (fMRI) datasets acquired during simulated driving task. The M-CCA method jointly decomposes fMRI
datasets from different subjects/sessions into brain activation maps and their associated time courses, such that the correlation
in each group of estimated activation maps across datasets is maximized. Therefore, the functional activations across all
datasets are extracted in the order of consistency across different dataset. On the other hand, M-CCA preserves the uniqueness
of the functional maps estimated from each dataset by avoiding concatenation of different datasets in the analysis. Hence,
the cross-dataset variation of the functional activations can be used to test the hypothesis of functional-behavioral association.
In this work, we study 120 simulated driving fMRI datasets and identify parietal-occipital regions and frontal lobe as the
most consistently engaged areas across all the subjects and sessions during simulated driving. The functional-behavioral association
study indicates that all the estimated brain activations are significantly correlated with the steering operation during the
driving task. M-CCA thus provides a new approach to investigate the complex relationship between the brain functions and multiple
behavioral variables, especially in naturalistic tasks as demonstrated by the simulated driving study. 相似文献