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Biomedical subjects

I Ludwig

Publications and source records attributed to I Ludwig.

18 recordsLinked to original sources

Expression of X-linked inhibitor of apoptosis as a novel prognostic marker in radically resected non-small cell lung cancer patients.

PURPOSE: To assess the pattern of expression and the prognostic value of the inhibitor of apoptosis family member X-linked inhibitor of apoptosis (XIAP; MIHA/ILP-a) in radically resected non-small cell lung cancer patients. EXPERIMENTAL DESIGN: The expression of XIAP and its relationship with overall survival was analyzed by immunohistochemistry on tumors from 144 patients with early-stage non-small cell lung cancer. In addition, the apoptotic and mitotic index, Ki-67, p53, and bcl-2 levels were also assessed. RESULTS: XIAP expression was specific for tumor cells, and the pattern was cytoplasmic. The median expression of XIAP was 20%, and when this value was used as a cutoff point for statistical analyses, 63 of the samples were considered high XIAP-expressing and 81 low XIAP-expressing. Surprisingly, high XIAP-expressing patients had a longer overall survival than the group expressing lower levels (60 versus 24 months of median survival; log rank, P = 0.01). The positive impact of XIAP expression on survival was confirmed by multivariate analysis (P = 0.026). Although no correlation was observed between XIAP expression and the apoptotic index, a significant inverse correlation was observed between XIAP, Ki-67 (P = 0.006), and mitotic index (P = 0.04). CONCLUSIONS: The unexpected inverse correlation of XIAP with proliferation markers and the absence of correlation with apoptotic index, coupled with its role as an independent positive prognostic factor for survival in radically resected NSCLC patients imply a more complex role for XIAP in tumor biology than anticipated by in vitro data.

Aged↗

Somatotopy of human hand somatosensory cortex revealed by dipole source analysis of early somatosensory evoked potentials and 3D-NMR tomography.

Somatosensory evoked potentials (SEPs) to median nerve and finger stimulation were analyzed by means of spatio-temporal dipole modelling combined with 3D-NMR tomography in 8 normal subjects. The early SEPs were modelled by 3 equivalent dipoles located in the region of the brain-stem (B) and in the region of the contralateral somatosensory cortex (T and R). Dipole B explained peaks P14 and N18 at the scalp. Dipole T was tangentially oriented and explained the N20-P20, dipole R was radially oriented and modelled the P22. The tangential dipole sources T were located within a distance of 6 mm on the average and all were less than 9 mm from the posterior bank of the central sulcus. In 6 subjects the tangential sources related to finger stimulation arranged along the central sulcus according to the known somatotopy. The radial sources did not show a consistent somatotopic alignment across subjects. We conclude that the combination of dipole source analysis and 3D-NMR tomography is a useful tool for functional localization within the human hand somatosensory cortex.

Adult↗

Source analysis of median nerve and finger stimulated somatosensory evoked potentials: multichannel simultaneous recording of electric and magnetic fields combined with 3D-MR tomography.

At the current state of technology, multichannel simultaneous recording of combined electric potentials and magnetic fields should constitute the most powerful tool for separation and localization of focal brain activity. We performed an explorative study of multichannel simultaneous electric SEPs and magnetically recorded SEFs. MEG only sees tangentially oriented sources, while EEG signals include the entire activity of the brain. These characteristics were found to be very useful in separating multiple sources with overlap of activity in time. The electrically recorded SEPs were adequately modelled by three equivalent dipoles located: (1) in the region of the brainstem, modelling the P14 peak at the scalp, (2) a tangentially oriented dipole, modelling the N20-P20 and N30-P30 peaks, and part of the P45, and (3) a radially oriented dipole, modelling the P22 peak and part of the P45, both located in the region of the somatosensory cortex. Magnetically recorded SEFs were adequately modelled by a single equivalent dipole, modelling the N20-P20 and N30-P30 peaks, located close to the posterior bank of the central sulcus, in area 3b (mean deviation: 3 mm). The tangential sources in the electrical data were located 6 mm on average from the area 3b. MEG and EEG was able to locate the sources of finger stimulated SEFs in accordance with the somatotopic arrangement along the central fissure. A combined analysis demonstrated that MEG can provide constraints to the orientation and location of sources and helps to stabilize the inverse solution in a multiple-source model of the EEG.

Adult↗

Preoperative localization of the central sulcus by dipole source analysis of early somatosensory evoked potentials and three-dimensional magnetic resonance imaging.

Surgery of lesions within or close to the central area of the brain always carries the risk of iatrogenic motor or sensory deficits. Functional localization by means of intraoperative direct stimulation of the motor area or by recording somatosensory evoked potentials (SSEP's) from the surface of the somatosensory cortex is believed to reduce the operative risk. The authors introduce the combination of dipole source analysis of scalp-recorded SSEP's with three-dimensional (3-D) magnetic resonance (MR) imaging as a tool for preoperative localization of the central sulcus. This provides information on both functional and structural localization for preoperative planning. Four repeated measurements of right and left median nerve SSEP's were obtained from 20 subjects. Dipole source analysis showed a retest reliability of the 3-D localization error of 2.9 +/- 2.0 mm. Compared to the MR evaluation, dipole source analysis was found to mark the central sulcus within 3 mm for 15 conditions (subjects x side of stimulation), while the 3-D MR measurement was accurate to within 6 mm for 10 conditions and 9 mm for 14 conditions. Dipole locations were confirmed in six patients who underwent surgery of the central region. With respect to this application, dipole source analysis combined with 3-D MR imaging appears to be a valuable tool for preoperative functional localization. The accuracy in localization will be further improved when realistic head models become available that can take into account individual head geometry. Further development of the proposed new method holds promise that evoked potentials and electroencephalography will gain greater use in presurgical functional localization.

Brain Diseases↗

[Topography of early cortical median nerve somatosensory evoked potentials: results for routine use of the method].

The results from a topographic analysis of the early median nerve SEPs allowed to design a method for recording and analysing the SEPs in the routine laboratory. The detailed analysis of the topography of 50 normal subjects revealed: 1. An inter- and intraindividual variability of the location of the maximal amplitudes, 2. A significantly longer latency of the cortical potentials after left side stimulation, 3. A significantly higher amplitude of N20 after left side stimulation and 4. A significantly higher amplitude of the later potentials P25 and N30 after right side stimulation. It was shown that a 4-channel recording from the neck at C7 with a Fz-reference as well as from stimulus contralateral F3, CP3 and P3 or F4, CP4 and P4 with an stimulus contralateral earlobe reference provides all necessary parameters in comparison to an 20-channel recording. The definition of normal values has to take into account these results. Absolute maximum values were taken instead of the standard deviation because all amplitude values were proven to be not distributed normally. In 7 out of 30 MCA-stroke patients pathological SEP amplitudes were obtained using the 4-channel montage, whereas the 1-channel recording from CP3 and CP4 with a Fz-reference revealed normal amplitudes.

Adult↗

Cardiorespiratory reflex responses to static contraction of vascularly isolated hindleg muscles of the rat.

One hindleg of an anasthetized rat (n = 15) was isolated from systemic blood circulation. The preparation was connected to the body only by nerve and bone. A. and V. femorales were cannulated and perfused with normoxic (PO2 = 530 mm Hg) or hypoxic (PO2 = 60 mm Hg) Tyrode solutions. Static contractions of the muscle were elicited by electrical stimulation on the sciatic nerve (2 x motor threshold, 400-800 mV, 50 s-1). A 1 s stimulus was followed by a 2 s rest period. Total test time amounted to 40 min. It was proceeded and succeeded by 20 min periods of control perfusions without stimulation. Heart rate (HR) and respiratory rate (f) were measured and cross correlated with the following outflow parameters from V. femoralis of the experimental muscle: [K+], [Na+], PO2, PCO2, pH and [lactate]. During the test period HR and f increased significantly within 20 min of the start of stimulation: HR 5.8% (p less than 0.005) and f 24.3% (p less than 0.005) for hypoxic perfusion (n = 6) and HR 3.2% (p less than 0.005) and f (p less than 0.001, ANOVA) for normoxic perfusion (n = 3). The dynamic changes of several outflow parameters were nearly simultaneous with the cardiorespiratory responses. Cross correlation analyses revealed an excellent temporal relationship between HR and PO2 or [lactate] and between f and PO2 or [lactate]. In addition PCO2 and pH correlated well with HR as well as with f. Comparison of the threshold of the cardiorespiratory response revealed an optimal relationship to pH, a good one to PCO2 and lactate concentration but no correlation to PO2.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Pathophysiological and clinical implications of thyroid growth-stimulating immunoglobulins: evidence for their intrathyroidal production.

Thyroid growth-stimulating immunoglobulins are responsible for goitre formation not only in Graves' and Hashimoto's disease but also (partly) in simple goitre, especially in recurrent cases. TGI are antibodies, the TSH receptor, however, appears not to be the antigenic site in simple goitre. In our own studies two TGI assay systems ([3H]thymidine incorporation into isolated porcine thyroid follicles and into FRTL-5 cells) gave comparable results. TGI was found in 20 out of 72 patients with simple goitre (27%) coming from an endemic goitre area (biased by selection, i.e. certainly including sporadic forms) and in 10 out of 26 patients (38%) with recurrent goitre. TGI levels were higher in thyroidal venous blood compared to cubital blood (simultaneously drawn during surgery) indicating an intrathyroidal production of TGI. Thyroid growth-blocking antibodies as estimated in the FRTL-5 cell assay in one of our patients might be of significance not only in primary myxoedema but also for congenital hypothyroidism.

Animals↗

Purification and properties of spinach leaf debranching enzyme.

Starch debranching enzyme was purified from intact spinach (Spinacia oleracea L. cv Vital) chloroplasts and from a spinach leaf extract using affinity chromatography on Sepharose 6B-bound cycloheptaamylose (Schardinger beta-dextrin). The enzyme from both sources was homogeneous upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Spinach leaf debranching enzyme appears to consist of a single polypeptide chain, since the molecular weight of the native protein (110,000 daltons) was not changed by treatment with sodium dodecyl sulfate. Only one spinach leaf debranching enzyme band could be detected after electrophoresis of a leaf extract on amylopectin-containing polyacrylamide gel, the retardation factor of which coincided with that of the single band seen with the chloroplast enzyme. The purified enzyme exhibited strong pullulanase activity, the specific activity being 69 units per milligram protein with pullulan and 22 units per milligram protein with amylopectin. Cycloheptaamylose is a potent competitive inhibitor of spinach leaf debranching enzyme. The pH optimum of the enzyme was found to be 5.5. The purified enzyme is rather unstable at both 20 degrees and 0 degrees C. Part of the activity lost under storage or at a suboptimal pH could immediately be restored by the addition of thiols. The reactivatable protein, being of the same molecular weight as the native enzyme, exhibited a somewhat altered electrophoretic mobility resulting in one or two minor bands on a zymogram.

Journal Article↗

Acute recurrent orbital myositis.

An acute relapsing orbital inflammatory disease predominantly affecting the extraocular muscles was seen in two patients and is reported here as acute recurrent orbital myositis. The association of this disorder with other systemic diseases such as asthma, sinusitis, upper respiratory infection, Crohn's disease, and serum sickness is discussed. The similarities to other forms of acute orbital inflammatory disease such as orbital pseudotumor are noted, and a possible underlying immunologic mechanism is suggested.

Acute Disease↗

Hemispheric asymmetries of early cortical somatosensory evoked potentials revealed by topographic analysis.

Scalp topography of the early cortical SEPs was analysed in 50 normal right handed subjects. The following hemispheric asymmetries of the potentials were found: 1) The maximal amplitude of N20 was located predominantly at the P electrode after right sided stimulation, but varied between the CP, P and O electrode after left sided stimulation. 2) The N20 amplitudes were higher after right sided stimulation in approximately 70% of the subjects and the P25 and N30 amplitudes were higher after left sided stimulation in again approximately 70% of the subjects. No side difference of amplitudes was found for the subcortical N14. The N20 amplitude and location asymmetries were attributed to an anatomical asymmetry of the somatosensory cortex.

Adult↗