[1st experiences with functional scintigraphy of tear ducts].
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Over the last three years, ascending, functional cine-phlebography has been used on 43 patients with different lesions of the venous system. The patient is placed in the decubitus dorsal position, on a radiological table inclined at 70 degrees. The opaque liquid is injected into the dorsal vein of the foot. Its movement is helped by the flexing of the muscles of the leg, and is followed on a screen. This method makes it possible to follow the morphological and functional aspects of the veins of the lower limbs. In this way it is possible to assess valvular function, the location of the perforating veins and their competence, the limits of a thrombosis, and the therapeutic results. This examination, which is painless and harmless, makes it possible to improve the precision of the diagnosis in patients with different vein lesions, and gives most valuable information on the functioning of the venous system of the lower limbs.
Functional insulin substitution, an insulin regimen made up of two daily injections of intermediate-acting insulin and prandial boluses of regular insulin, was to be introduced in 49 type 1 diabetic patients, as previous regimens consisting of two or three daily injections proved to be inefficient due to the patients lifestyle or inherent metabolic lability. Forty-five patients were treated with human insulin injected by NovoPen. In 38 cases therapy was changed in the frame of a one-week, small-group, inpatient, structured educational course. After a mean 14 months of follow-up metabolic status improved in 33 cases while there was further derangement in 16. Eighteen patients were practising true functional therapy, i.e. doing blood glucose tests before each injection. Further 22 diabetics were trying to achieve better metabolic control through 2-3 daily blood glucose tests and insulin dose corrections. The metabolic status was not affected by the frequency of blood glucose testing, rather by raising of the daily dose of short acting insulin in conjunction with the switch in therapy acting beneficially. All patients insisted on using NovoPen further on.
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Functional insulin substitution, an insulin regimen made up of two daily injections of intermedier acting insulin and prandial boluses of regular insulin, was to be introduced in 49 type 1 diabetic patients, as previous regimens consisting of two or three daily injections proved to be inefficient due to the patients' lifestyle or inherent metabolic lability. 45 patients were treated with human insulin injected by NovoPen. In 38 cases therapy was changed in the frame of a one-week, small-group, inpatient, structured educational course. After a mean 14 months of follow-up metabolic status improved in 33 cases while there was further derangement in 16. 18 patients were practicing true functional therapy ie. doing blood glucose tests before each injection. Another 22 diabetics were trying to achieve better metabolic control through 2-3 daily blood glucose tests and insulin dose corrections. Metabolic status was not affected by the frequency of blood glucose testing, rather by the raising of the daily dose of Actrapid insulin in conjunction with the switch in therapy acting beneficially. All patients insisted on using NovoPen further on.
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To gain more information about sources of activator Ca2+ involved in the contraction of rat and guinea-pig aorta evoked by angiotensin II and their sensitivity to Ca2+ entry blockers, measurement of slowly exchanging 45Ca2+ was established. A more physiological procedure was used, replacing La(3+)- and EGTA-containing solutions by a normal Ca(2+)-containing buffer. It was demonstrated that the angiotensin II-induced increase in slowly exchanging 45Ca2+ in rat aorta was incompletely (by approximately 60%-70%) inhibited by the organic Ca2+ entry blockers nifedipine, verapamil and diltiazem and by other Ca2+ entry blocking compounds like CoCl2 and chlorpromazine. 8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride (TMB-8) was able to inhibit the angiotensin II-induced increase in 45Ca2+ content completely, but this may be an intracellular storage effects. By contrast, the organic Ca2+ entry blockers completely inhibited that part of the angiotensin II-induced contraction of rat aorta which was dependent upon extracellular Ca2+. In guinea-pig aorta, the increase in 45Ca2+ content elicited by angiotensin II could be completely suppressed by all compounds under study. The results of these experiments correlated well with data from the functional experiments in guinea-pig aorta. In both preparations the release of Ca2+ from a rapidly as well as a slowly exchanging intracellular pool appears to contribute to the contractile response elicited by angiotensin II.
BACKGROUND: Glycosylation and long non-coding RNAs (lncRNAs) play critical roles in tumor progression. However, the prognostic significance of glycosylation-related lncRNAs (GRLncs) in kidney renal clear cell carcinoma (KIRC) remains largely unclear. This study aimed to identify prognostic GRLncs and construct a predictive model for KIRC prognosis. METHODS: Transcriptomic and clinical data of KIRC patients were analyzed to identify GRLncs associated with overall survival (OS). A prognostic model was constructed based on selected GRLncs, and its predictive performance was evaluated using Kaplan-Meier (KM) survival analysis, receiver operating characteristic (ROC) curves, and univariate and multivariate Cox regression analyses. Patients were stratified into high- and low-risk groups according to the median risk score, and internal validation was performed using training and testing cohorts to assess the stability of the model. Tumor microenvironment characteristics, immune checkpoint expression, immunotherapy response, and drug sensitivity were further analyzed. In addition, the expression of three signature lncRNAs was validated by real-time quantitative polymerase chain reaction (RT-qPCR) in 10 paired KIRC tumor and adjacent normal tissues. Functional roles of selected lncRNAs were investigated using antisense oligonucleotides (ASOs)-mediated knockdown in KIRC cell lines, followed by Cell Counting Kit 8 (CCK-8), 5-ethynyl-2'-deoxyuridine (EdU) incorporation, colony formation, and migration assays. RESULTS: Five GRLncs (AC093278.2, EPB41L4A-DT, DLGAP1-AS2, AC084876.1, and AC005261.3) were identified and used to construct a prognostic model. AC093278.2 and EPB41L4A-DT were protective factors, whereas DLGAP1-AS2, AC084876.1, and AC005261.3 were risk factors. KM analysis on GRLncs-based risk score stratification revealed patients in the high-risk group had significantly poorer OS than those in the low-risk group. ROC analysis and Cox regression demonstrated that the GRLnc-based risk score served as an independent predictor of KIRC prognosis and exhibited favorable predictive performance compared with conventional clinical variables. High- and low-risk groups also exhibited distinct immune microenvironment characteristics, immune checkpoint expression patterns, and predicted drug sensitivities. RT-qPCR detected significant downregulation of protective factor-EPB41L4A-DT in KIRC tissues, while risk factors-DLGAP1-AS2 and AC084876.1 showed expression trends consistent with their predicted risk attributes. Functional experiments further revealed that knockdown of DLGAP1-AS2 and AC084876.1 suppressed proliferation and migration of KIRC cells, whereas knockdown of EPB41L4A-DT promoted these processes, supporting the biological relevance of these three signature lncRNAs. CONCLUSIONS: This study establishes a novel prognostic model based on five GRLncs that showed promising performance in The Cancer Genome Atlas (TCGA)-based analyses of KIRC. The combined clinical expression analysis and functional validation of three constituent GRLncs (DLGAP1-AS2, EPB41L4A-DT, and AC084876.1) supports the biological plausibility of the model and suggest that GRLncs may serve as potential prognostic biomarkers and therapeutic targets for KIRC.
Three different central auditory skills were compared and evaluated in 56 blind and 40 sighted subjects. The study consisted of three experiments conducted in three subgroups. Experiment A was performed in order to evaluate the localization function; experiment B for the temporal auditory resolution ability of the blind adult, and experiment C to test the ability of the blind person to discriminate speech material in noise. In all three experiments the blind subjects obtained significantly better results than the sighted subjects. From these results it was concluded that there is supporting evidence of a certain superiority of the blind individual with regard to central auditory function.
Determinations of apparent equilibrium dissociation constants of drug-receptor interactions are made from both functional and radioligand binding studies. In each type of study, reversible reactions are assumed and the mass action law is applied. Functional studies are frequently used to determine the dissociation constant of a competitive antagonist but are less frequently used to obtain this constant for agonist compounds since the latter determination requires an experimental procedure that irreversibly inactivates a fraction of the receptors. In the present report, values of dissociation constant for prototype agonists and antagonists, determined from binding and from functional studies, are examined in two classical isolated preparations, rabbit aorta and guinea-pig ileum. In each preparation the dissociation constants from binding and functional experiments agree well for the antagonists but differ markedly for the agonists. Further, the dissociation constant values from binding are seen to be greater for the agonists than for the antagonists. When a chronic treatment regimen in the rabbit resulted in a pronounced change in the functional dissociation constant of subsequently administered norepinephrine, there was no significant change in either the binding constant of this agonist or in the pA2 value of the alpha antagonist, phentolamine. These, and the previously described results, are shown to be compatible with a simple two-state receptor model in which agonists bind with high and low affinity to each state while antagonists do not distinguish between the states. In this model, the ratio of low to high affinity states accounts for the failure of the binding procedure to detect changes in the agonists dissociation constant that are highly significant in the functional study. Whereas the model is based on data for these two classical preparations only, and may not be more generally applicable, the findings demonstrate the necessity for employing both functional and radioligand binding experiments when characterizing drug receptors.
Effects of electrical and chemical stimulations of the frontal and fronto-parietal cortex on behaviour of rats and functional state of the brain-stem inhibitory centers, was studied in chronic experiments. Functional influences of rostral cortex on the brainstem structures was shown.
We present a model of integrated psychotherapy of schizophrenia. When we do an integrated therapy with a patient, attention must always be directed to the calibration of the interventions which constitute the therapeutic compound. This kind of calibration has to be done by a therapist with an integrative function. Experience and competence are necessary conditions, but not sufficient ones for carrying out such a function; the therapist must have also the authority which is due not only to his hierarchic role, but which has to be empathically recognized by the other therapists and the patient. The theoretical reflection has been possible only by starting from a clinical experience (the case of a young woman who in the light of the nosographical categories was considered an 'impossible patient') which allowed us to translate the clinical language into a conceptual form.
Gastric cancer remains a leading cause of cancer-related mortality worldwide, and the identification of clinically relevant biomarkers is critical for improving patient outcomes. Oxidized low-density lipoprotein receptor 1 (OLR1) has been implicated in tumor progression; however, its role in gastric cancer and the tumor microenvironment remains unclear. OLR1 expression and clinical significance were analyzed using The Cancer Genome Atlas (TCGA) dataset and validated in gastric cancer cell lines. Gain- and loss-of-function experiments, together with in vitro and in vivo assays, were performed to investigate the biological functions and underlying mechanisms of OLR1 in gastric cancer progression. OLR1 was significantly upregulated in gastric cancer and associated with unfavorable prognosis. Functional analyses demonstrated that OLR1 promoted gastric cancer cell proliferation, migration, and tumor growth. Mechanistically, OLR1 activated NF-κB signaling and facilitated macrophage polarization toward the M2 phenotype, thereby contributing to a protumorigenic microenvironment. OLR1 promotes gastric cancer progression through activation of NF-κB signaling and modulation of macrophage polarization. These findings identify OLR1 as a potential prognostic biomarker and therapeutic target for gastric cancer.
beta- And alpha 1-adrenoceptor antagonist properties of bufuralol, carvedilol, celiprolol, dilevalol, labetalol, and pindolol were investigated in human myocardium and mammary artery using binding techniques and functional studies. In myocardial membranes, beta-adrenoceptor antagonists showed monophasic competition isotherms for [125I]pindolol binding with high affinity (Ki from 1-100 nM), except for celiprolol which displayed a biphasic competition isotherm (pKi = 6.4 +/- 0.06 for beta 1- and 4.8 +/- 0.07 for beta 2-adrenoceptors). Drug interactions with alpha 1-adrenoceptors were evaluated in human mammary artery by [3H]prazosin binding and by measuring contractile responses to norepinephrine (NE). Labetalol and carvedilol showed a moderate affinity for alpha 1-adrenoceptors (pKi = 6.2 +/- 0.01 and 6.1 +/- 0.06, respectively), and inhibited NE-induced contractions (pA2 = 6.93 +/- 0.23 and 8.64 +/- 0.24, respectively). Dilevalol, bufuralol, and pindolol displayed weak effect both in binding (Ki in micromolar range) and functional experiments (pA2 = 5.98, 5.54, and 6.23, respectively). Celiprolol did not show antagonist properties up to 100 microM in functional studies, but displayed a slight affinity for alpha 1-adrenoceptors in binding studies. The data indicate that the vasodilating activity of these beta-adrenoceptor antagonists is caused in some instances by an alpha 1-adrenoceptor antagonism (labetalol, carvedilol), whereas for the others alternative mechanisms should be considered.
Experiments with invertebrate animals offer valuable opportunities in the teaching of physiology. In some cases, exercises that use these animals may demonstrate physiological principles more clearly than experiments that use vertebrates. Other experiments are easy to perform because of the latitude of conditions in which the tissues of many invertebrates function. Experiments with invertebrates can also illustrate a far wider range of physiological mechanisms than occurs in vertebrates and are especially suited for opportunities for independent original investigation by the students. Since at this time invertebrates are underutilized in teaching, much can be gained by the design, testing, and dissemination of innovative experimental protocols for student use.