104,635 research outputs found
Desensitization of insulin secretory response to imidazolines, tolbutamide, and quinine II. Electrophysiological and fluorimetric studies
No full textProlonged in vitro exposure (18 h) of pancreatic islets to insulin secretagogues that block ATP-dependent K+ channels (K-ATP channels). such as sulfonylureas. imidazolines, and quinine, induced a desensitization of insulin secretion (Rustenbeck et al., pages 1685-1694, this issue). To elucidate the underlying mechanisms. KATP channel activity, plasma membrane potential and the cytosolic Ca2+ concentration ([Ca2+](i)) were measured in mouse single B-cells. In B-cells desensitized by phentolamine or quinine (100 muM each) KATP channel activity was virtually absent and could not be elicited by diazoxide. Desensitization by alinidine (100 muM) induced a marked reduction of KATP channel activity, which could be reversed by diazoxide, whereas exposure to idazoxan (100 muM) or tolbutamide (500 muM) had no lasting effect on K-ATP channel activity. Correspondingly. phentolamine, alinidine, and quinine-desensitized B-cells were markedly depolarized, whereas B-cells that had been exposed to tolbutamide or idazoxan had an unchanged resting membrane potential. The increase in [Ca2+](i) normally elicited by phentolamine and alinidine was suppressed after desensitization by these compounds., whereas the [Ca2+](i) increase by re-exposure to quinine was markedly reduced and that by tolbutamide only minimally affected as compared with control-cultured B-cells. The increase in [Ca2+](i) elicited by a K+ depolarization was diminished in secretagogue-pretreated B-cells. the extent depending on the secretagogue. This effect was closely correlated with the degree of depolarization after pretreatment with the respective secretagogue. In conclusion, the apparently uniform desensitization of secretion by K-ATP channel blockers is due to different effects at two stages located distally in the stimulus-secretion coupling: either at the stage of [Ca2+](i), regulation, where the increase is depressed as a consequence of a persistent depolarization (e.g. in the case of phentolamine or alinidine) and/or at the stage of exocytosis. which responds only weakly to substantial increases in [Ca2+](i) (in the case of tolbutamide). (C) 2001 Elsevier Science Inc, All rights reserved
Desensitization of insulin secretory response to imidazolines, tolbutamide, and quinine I. Secretory and morphological studies
No full textThe desensitization of pancreatic B-cells against stimulation by insulin secretagogues that inhibit ATP-dependent K+ channels (K-ATP channels) was investigated by measuring insulin secretion of perifused pancreatic islets. Additionally, the islet insulin content and the number of secretory granules per B-cell were determined. Prior to the measurement of secretion, islets were cultured for 18 h in the presence or absence of the test agents in a cell-culture medium containing 5 mM glucose. The effects of three imidazolines, phentolamine, alinidine, and idazoxan (100 AM each) were compared with those of the well-characterized sulfonylurea. tolbutamide (500 AM), and those of the ion channel-blocking alkaloid, quinine (100 AM). Insulin secretion was strongly reduced upon re-exposure to phentolamine, alinidine, tolbutamide, and quinine, whereas idazoxan, which stimulated secretion only weakly, had no significant effect. The imidazoline secretagogues phentolamine and alinidine induced a cross-desensitization against the stimulatory effect of tolbutamide and quinine. A long-term depolarization with 40 mM KCl was also able to induce a significant reduction of the secretory response to all of the above secretagogues. The insulin content of cultured islets was moderately, but significantly reduced by alinidine, whereas the reduction by phentolamine, tolbutamide, and quinine was not significant. In contrast to these observations, the ultrastructural examination revealed that tolbutamide-treated B-cells had a high degree of degranulation, whereas the other test agents and 40 mM KCl produced only a partial degranulation, except for phentolamine, which produced no significant degranulation at all. These results suggest that the desensitization of insulin secretion is a common property of all agents that stimulate insulin secretion by depolarisation of the plasma membrane. Depending on the specific secretagogue, additional mechanisms, proximal and distal to Ca2+ influx, appear to contribute to the desensitization (see Rustenbeck et al., pages 1695-1703, this issue). (C) 2001 Elsevier Science Inc. All rights reserved
A comparison of angiographic CT and multisection CT in lumbar myelographic imaging
No full textBACKGROUND AND PURPOSE: The purpose of this work was to provide an intraindividual comparison of angiographic CT (ACT) and multisection CT (MSCT) in lumbar myelographic imaging and to evaluate possible benefits of ACT, which is a further development of rotational angiography providing image data of high spatial and CT-like contrast resolution. MATERIALS AND METHODS: In 26 patients with degenerative lumbar spine disease a lumbar ACT was performed in combination with conventional lumbar myelography and followed by postmyelographic. MSCT. Conventional lumbar myelography and lumbar ACT were performed with a flat panel detector-equipped angiographic device. Postmyelographic MSCT was performed with a 16-section CT scanner. Three experienced neuroradiologists rated anonymized sets of multiplanar reformatted CT and ACT images regarding diagnostic and technical parameters. The ratings were repeated after 2 months. Weighted K Statistics were calculated to describe the levels of intraobserver and interobserver agreement. RESULTS: The analysis shows that MSCT achieves higher ratings than ACT in all of the parameters asked. An adequate diagnostic quality was only assigned to 80% of the ACT acquisitions compared with 97% of the MSCT acquisitions. All of the mean K values were above 0.60, demonstrating a substantial intraobserver and interobserver agreement for MSCT, as well as for ACT. CONCLUSION: Using ACT, radiographic myelography and myelographic CT can be performed at the same imaging system. However, the results of our study show that the current myelographic ACT image quality fails to apply diagnostic standards. We, therefore, cannot recommend ACT as a general alternative to postmyelographic MSCT
Polyneuropathy as a sole syndrome in mialignant thymoma
No full textUp to 40% of patients with malignant thymoma suffer from paraneoplastic symptoms (90% myasthenia, 10% other symptoms). A 55-year-old patient developed ascending symmetrical, sensorimotor tetraparesis. A malignant thymoma without metastases was diagnosed 6 months, later. Despite thymectomy followed by radiation and high-dose corticosteroid therapy, the, polyneuropathy progressed. Six months after onset, the patient was bound to a wheelchair. Immunosuppressive therapy with cyclophosphamide was initiated, leading to marked remission. After ten cycles, the patient was able to walk independently with walking aids. After the sixth and tenth cycle, respectively, attempts to discontinue immunosuppression led to relapse. In several diagnostic workups, however, there was no tumour relapse. After 13 cycles, cyclophosphamide was replaced by immunoglobulins (0.4 g/kg per day i.v. for 5 days/month) due to progressive renal failure. The patient died just before the secondcourse of this treatment. In conclusion, in the differential diagnosis of rapidly progressive polyneuropathy a malignant thymoma should be considered, even in the absence of myasthenia. Immunosuppression with cyclophosphamide resulted in amelioration of symptoms in this patient
The approximate planimetric method: a simple, rapid and reliable method for estimation of lesion size in acute ischemic stroke
No full textMagnetic resonance imaging is increasingly used in stroke trials for early diagnosis and follow-up of lesion size. Since volumetric measurement remains a laborious and time-consuming task, a rapid and reliable method for the assessment of lesion size has been developed and validated in diffusion weighted imaging (DWI) and fluid attenuated inversion recovery (FLAIR) sequences. These were serially obtained in 40 patients less than 8 h after the onset of symptoms of a middle cerebral artery territory stroke (day 1), as well as on days 3 and 18. For each of 16 (DWI) or 20 (FLAIR) transverse sections obtained on each occasion, lesion size was estimated as a percentage of the total hemisphere. Percentage values from all sections were summed up and expressed as arbitrary units. Results obtained using this approximate planimetric method (APM) were compared with those from a standard volumetric approach. Lesion volumes as determined by both methods were highly correlated (DWI: r=0.966, FLAIR: r=0.979, p<0.001). To conclude, the APM is simple, rapid and reliable for the estimation of lesion size in acute ischemic stroke. It can be recommended for broader application in clinical trials
Going Beyond Counting First Authors in Author Co-citation Analysis
No full textThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
beta-cell toxicity of ATP-sensitive K+ channel-blocking insulin secretagogues
No full textA prolonged exposure of isolated pancreatic islets to insulin secretagogues, the imidazolines phentolamine, alinidine and idazoxan (100 muM each), the sulfonylurea tolbutamide (500 muM), or the alkaloid quinine (100 muM) resulted in morphological damage of 4-18% of beta-cells compared to less than 2% in controls. Thus, the question arose whether K-ATP channel-blocking insulin secretagogues are beta-cell toxic as has already been suggested for sulfonylureas. The concentration- and time-dependency of the secretagogue-associated toxicity was documented by viability assays in insulin-secreting HIT T15 cells. Treatment for 24 h with idazoxan reduced MTT conversion by 50% at 100 muM and by 98% at 1000 muM. Phentolamine and quinine reduced viability comparably at 1000 muM, but were less toxic at 100 muM. On the other hand, the imidazoline alinidine and the sulfonylurea tolbutamide were only moderately toxic (less than 40% viability loss at 1000 muM). The imidazoline efaroxan appeared even to be non-toxic. Apoptotic DNA fragmentation and DEVD-caspase activation was observed at 100 muM of idazoxan and phentolamine, whereas at 1000 muM signs of necrosis predominated. Alinidine, tolbutamide and quinine treatment did not increase markers of apoptotic cell death. Blocking Ca2+ influx by D600 did not diminish secretagogue-associated toxicity. Electron microscopy confirmed the validity of these observations for beta-cells in intact mouse islets. In summary, beta-cell toxicity of the tested insulin secretagogues varied widely and did not depend on a prolonged Ca2+ influx via L-type Ca2+ channels. Thus, secretagogue-mediated closure of K-ATP channels is apparently not per se beta-cell toxic. (C) 2004 Elsevier Inc. All rights reserved
Appropriate Similarity Measures for Author Cocitation Analysis
No full textWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Case-report: BSE-like symptoms in a cow actually caused by a malignant nerve sheath tumor
No full textWe report here on a 3 1/2-year-old mother cow with a malignant perineural tumour near the pontine angle of the cerebellum, but which first drew attention because of clinical signs of BSE. Neurological symptoms that manifested during the course of the disease included disturbances in behaviour, movement and aesthesia, as described by BRAUN et al.(2001) in cases of BSE. Inconsistent with a diagnosis of BSE were focal neurological disturbances (head held aslant to the right, tendency to fall to the right, right-sided facial weakness, left-sided nystagmus and ventral strabismus). Following euthanasia, magnetic resonance imaging (MRI) revealed a tumour in the cerebellopontine angle. Histological findings describe a malignant peripheral nerve tumour of the vagal nerve with rhabdoid differentiation (a so-called Triton tumour) with an intracranial and an extracranial part
Case-report: BSE-like symptoms in a cow actually caused by a malignant nerve sheath tumor
No full textWe report here on a 3 1/2-year-old mother cow with a malignant perineural tumour near the pontine angle of the cerebellum, but which first drew attention because of clinical signs of BSE. Neurological symptoms that manifested during the course of the disease included disturbances in behaviour, movement and aesthesia, as described by BRAUN et al.(2001) in cases of BSE. Inconsistent with a diagnosis of BSE were focal neurological disturbances (head held aslant to the right, tendency to fall to the right, right-sided facial weakness, left-sided nystagmus and ventral strabismus). Following euthanasia, magnetic resonance imaging (MRI) revealed a tumour in the cerebellopontine angle. Histological findings describe a malignant peripheral nerve tumour of the vagal nerve with rhabdoid differentiation (a so-called Triton tumour) with an intracranial and an extracranial part
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