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Biomedical subjects

P Steiner

Publications and source records attributed to P Steiner.

At least 37 records · Page 2Linked to original sources

Syntaxin 13 is a developmentally regulated SNARE involved in neurite outgrowth and endosomal trafficking.

In addition to its role in exocytosis, SNAP-25 is essential for axonal outgrowth. In order to identify SNARE proteins involved in neurite growth we have used SNAP-25 antibodies to affinity-purify protein complexes enriched in developing rat brain membrane extracts. We have identified a complex between SNAP-25 and syntaxin 13 predominantly present in brain at embryonic or early postnatal stages. We show that syntaxin 13 is developmentally regulated with a decrease in adult brain. In differentiated neuroendocrine PC12 cells as well as primary cortical neurons the protein is localized to a punctated and tubular staining in the perinuclear region and along processes with high levels in the central region of growth cones. Carboxy-terminally tagged syntaxin 13 was also detected on the plasma membrane by in vivo surface-labelling where it colocalized with SNAP-25. Syntaxin 13 has recently been shown to be implicated in early endosomal trafficking. In our study, colocalization with internalized transferrin in the cell body and along neurites confirmed endosomal location in both compartments. Finally, overexpression of full-length syntaxin 13 enhanced neurite outgrowth in NGF-stimulated PC12 cells, whilst it had no effect on regulated secretion. The data suggest that a syntaxin 13-dependent endocytic trafficking step plays a limiting role in membrane expansion during neuronal development.

Age Factors↗

Long-term excessive magnesium supplementation is deleterious whereas suboptimal supply is beneficial for bones in rats.

The long-term effects of a suboptimal magnesium supply inducing a marginal or moderate deficiency or of an excessive magnesium supplementation corresponding to a basal diet with a high pharmacological intake were investigated in 36 growing Sprague-Dawley female rats. The rats were randomly divided in three groups and received a purified diet with 7 g calcium, 5 g phosphorus and either 0.2, 0.5 or 2 g magnesium per kg diet for 7 months. At the end of the trial, plasma and erythrocyte total magnesium concentrations were significantly lower in the magnesium-deficient group than in the respective control group. Serum concentrations of 1,25-dihydroxyvitamin D, PTH and IGF-I and the length of the right humeri were not affected by the dietary treatment. The volumes corrected for body weight, the medio-lateral diameters and the ratios dry weight/length of the right humeri, and the dry weight corrected for body weight of the left tibiae and of the right humeri were significantly smaller in the magnesium-supplemented group than in the two other groups. The magnesium contents of the left tibiae and of the first lumbar vertebrae were significantly lower in the magnesium-deficient group than in the two other groups. In the right femora, dual energy X-ray absorptiometry revealed significantly smaller areas in the proximal part and significantly smaller mineral contents in the second proximal quarter in the magnesium-supplemented group compared with the two other groups. Peripheral quantitative computer tomography of the right humeri revealed in the cortex significantly larger values for the relative area, mineral content, mineral density and thickness in the magnesium-deficient group compared with the control group. The maximum point of the load-deformation curve was significantly reduced in the fifth lumbar vertebrae and in the proximal femoral metaphyses of the magnesium-supplemented group. These results indicate that the long-term suboptimal magnesium supply improved some of the parameters indicators of bone health whereas the long-term supplementation was deleterious.

Animals↗

[Importance of digital thoracic radiography in the diagnosis of pulmonary infiltrates in patients with bone marrow transplantation during aplasia].

PURPOSE: Evaluation of digitized chest x-ray for the detection of pulmonary infiltrations in bone marrow transplant patients during aplasia. METHODS: Digitized chest x-rays of 40 patients (21 female, 19 male) with "Fever of unknown origin" (FUO) were evaluated concerning radiological signs of pulmonary infiltrations and correlated to clinical findings, blood chemistry, microbiology and bronchoscopy. Additionally, an individual risk profile was established. RESULTS: In 11/40 patients pulmonary infiltrations were detected in digitized chest x-rays (group 1). 10/11 developed an infectious pulmonary infiltration. 29/40 patients developed no pulmonary infiltration (group 2). When fever increased for the first time (initial chest x-ray) a sensitivity, specificity, positive and negative predictive value of 46%, 86%, 56%, 81% and for the chest x-rays in progress of 61%, 79% 68% and 73% was found. C-reactive protein and temperature increase occurred statistically significantly earlier (p < 0.05) in group 1 compared to group 2. The average latency of digital chest x-rays in comparison to c-reactive protein and temperature increase was 6 days. The incidence of risk factors was significantly higher in group 1 in comparison to group 2 (p < 0.05). CONCLUSION: Digitized chest x-rays are not a reliable method for primary detection of pulmonary infiltrations after bone marrow transplantation. Individual risk factors have to be taken into consideration to indicate further diagnostic methods such as computed tomography at an earlier time.

Adult↗

Locoregional regulatory peptide receptor targeting with the diffusible somatostatin analogue 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC): a pilot study in human gliomas.

Human gliomas, especially of low-grade type, have been shown to express high-affinity somatostatin receptor type 2 (J-C. Reubi et al., Am. J. Pathol, 134: 337-344, 1989). We enrolled seven low-grade and four anaplastic glioma patients in a pilot study using the diffusible peptidic vector 90Y-labeled DOTA0-D-Phe1-Tyr3-octreotide (DOTATOC) for receptor targeting. The radiopharmakon was locoregionally injected into a stereotactically inserted Port-a-cath. DOTATOC competes specifically with somatostatin binding to somatostatin receptor type 2 in the low nanomolar range as shown by a displacement curve of 125I-[Tyr3]-octreotide in tumor tissue sections. Diagnostic (111)In-labeled DOTATOC-scintigraphy following local injection displayed homogeneous to nodular intratumoral vector distribution. The cumulative activity of regionally injected peptide-bound 90Y amounted to 370-3300 MBq, which is equivalent to an effective dose range between 60 +/- 15 and 550 +/- 110 Gy. Activity was injected in one to four fractions according to tumor volumes; 1110 MBq of 90Y-labeled DOTATOC was the maximum activity per single injection. We obtained six disease stabilizations and shrinking of a cystic low-grade astrocytoma component. The only toxicity observed was secondary perifocal edema. The activity:dose ratio (MBq:Gy) represents a measure for the stability of peptide retention in receptor-positive tissue and might predict the clinical course. We conclude that SR-positive human gliomas, especially of low-grade type, can be successfully targeted by intratumoral injection of the metabolically stable small regulatory peptide DOTATOC.

Adult↗

Interactive volume visualization using "intelligent movies".

High quality visualization of medical volume models as performed by the VOXEL-MAN and similar systems is still too time consuming and the interaction complicated when sophisticated tools like dissection are used. We hence developed a new paradigm allowing to create simpler derivatives of the model, called "intelligent movies". These are in QuickTime or QuickTime VR format which allow interactive exploration with two degrees of freedom. As a decisive novelty, we extended it by a pixelwise link to the knowledge base which may be queried in the image context. Thus scenes emphasizing a selected aspect of the volume model may be created as intelligent movies, which a user (referring physician, student) can explore largely with the functionality of VOXEL-MAN, but in real time--on any standard PC--and also via a JAVA applet within web browsers. This is shown with the example of 3D interactive anatomical atlases and clinical cases.

Anatomy, Cross-Sectional↗

Cloning and expression of the Zymomonas mobilis pyruvate kinase gene in Escherichia coli.

The homotetrameric pyruvate kinases (PK) constitute a fine example of allosteric enzymes subjected to sophisticated regulatory mechanisms. We have cloned and sequenced the Zymomonas mobilis structural gene for the first prokaryotic dimeric PK, as an initial step toward understanding the peculiar properties of this enzyme. The deduced amino acid sequence of the pyk gene consists of 475 residues with a calculated molecular mass of 51.4kDa and exhibits up to 50% sequence identity with other PKs. Heterologous expression in Escherichia coli was not obtained from the native promoter, but only when the pyk gene was under the control of a strong inducible promoter when a ribosome-binding site was present upstream of the putative TTG start codon of the pyk gene. Kinetic characterization of PK in concentrated crude cell extracts showed that the enzyme is not activated by sugar phosphates or AMP but is slightly inhibited by ATP. Thus, PK of Z. mobilis is unique among the characterized prokaryotic PKs due to its high activity in the absence of any allosteric activator. Amino acid sequence alignments revealed that glutamate 381 may play a role in ineffective binding of the usual PK activator, fructose-1,6-bisphosphate.

5' Untranslated Regions↗

Tissue-independent MR tracking of invasive devices with an internal signal source.

An improved MR tracking coil design is described that provides more robust tracking performance. It is shown theoretically and experimentally that a coil equipped with an internal spin source increases the signal-to-noise ratio in comparison to a coil system without internal source. The tracking behavior is stable even in air, which is important for laparoscopic work, in which the device has to be placed inside the inflated abdomen. Two types of coil windings were tested: one with the windings perpendicular to the coil axis and the other one with the windings tilted relative to this axis. The experiments showed no significant effect on the signal-to-noise ratio between the two types. The improved MR-tracking coil design with internal source was successfully used in cholecystostomies and in laparoscopic interventions; both procedures were performed on swine.

Animals↗

MR guidance of laser disc decompression: preliminary in vivo experience.

The purpose of this study was to perform percutaneous laser disc decompression (PLDD) under MR guidance in an open configuration 0. 5-T MR system. Following failed conservative treatment for 6 months, eight patients with contained disc herniations were enrolled in the study. Following MR guided introduction of the laser fiber into the targeted disc space, the laser-induced temperature distribution was visualized using a color-coded subtraction technique based on a T1-weighted GRE sequence. In seven patients PLDD could be performed. In all cases laser effects were depicted by MR. In this regard the color-coded technique was found to be superior to conventional magnitude images. Whereas no apparent decrease in the extent of herniation was discovered immediately following PLDD, T2-weighted FSE images showed signal intensity alterations in two of the seven patients. Clinical evaluation, obtained 3-4 months after PLDD, revealed a fair (n = 2) or good (n = 4) response to the treatment. One patient showed no change in symptoms. MR guidance and monitoring of PLDD is feasible within an open 0.5-T system and seems to render PLDD more safe and controllable.

Adult↗

Interactive MR-guided biopsies of the thyroid gland: validation of a new method.

The aim of this study was to demonstrate the clinical feasibility and utility of an interactive MR-guidance system to target and biopsy thyroid lesions, and to compare resolution between ultrasound and interventional MR imaging in the evaluation of thyroid lesions. Twenty thyroid lesions of 18 patients were interactively biopsied using a 0.5-T superconducting open magnet system. Stereotactic localization of the needle and imaging was accomplished using T1-weighted gradient-recalled-echo (GRE) images. Representative cytological material was retrieved in 16 of 20 lesions (benign cystic or colloid goiter: n = 14; one de Quervain's thyroiditis and one follicular neoplasia). Lesions smaller than 1.5 cm detected by ultrasound could not be visualized adequately on GRE images. Lesions smaller than 1.5 cm were successfully biopsied by ultrasound (three colloid and haemorrhagic goiters and one adenoma). Magnetic-resonance-guided interactive biopsies and positioning of non-ferromagnetic needles in the thyroid gland are technically feasible and safe. Compared with high-resolution ultrasound, lesions larger than 1.5 cm can be adequately visualized and biopsied. Magnetic-resonance-guided placement of non-ferromagnetic needles is no substitute for high-resolution ultrasound in clinical work-up of thyroid lesions.

Biopsy, Needle↗

Optimization of contrast dosage for gadolinium-enhanced 3D MRA of the pulmonary and renal arteries.

To determine the minimal contrast dosage required for diagnostic contrast-enhanced three-dimensional (3D) magnetic resonance angiography (MRA) image quality of the pulmonary (PAs) or renal arteries (RAs). In 12 volunteers (10 females, 2 males; mean age 24 years) imaging was performed with 4 different dosages: 0.05, 0.1, 0.2 and 0.3 mmol/kg of body weight (BW) 0.5 M gadolinium (Gd) contrast agent. The PAs and RAs were evaluated separately each in groups of six volunteers. Qualitative and quantitative signal-to-noise ratio (SNR) image analysis was performed. For the PAs, the increases in signal-to-noise ratio were paralleled by increases in image quality ratings. For the PAs, with the use of 0.05 mmol/kg, only 50.3% of all segments were rated diagnostic, whereas with higher dosages the percentage rose to 89.2% for 0.1 mmol/kg, 98.2% for 0.2 mmol/kg. and 99.1% for 0.3 mmol/kg. For the RAs, 0.3 mmol/kg provided no significant increase in singal-to-noise ratio compared to 0.2 mmol/kg (p = 0.4). Only by a dosage of 0.2 and 0.3 mmol/kg, all evaluated segments were diagnostic evaluable. A dose of 0.2 mmol/kg is required for proper assessment of the RAs or PAs.

Adult↗

[Transmyocardial laser revascularization--the initial experiences of imaging in MRT].

PURPOSE: Imaging of myocardial signal alteration and perfusion differences after transmyocardial laser revascularization (TMLR). METHODS AND MATERIAL: 5 patients suffering from coronary vessel disease underwent MRI (0.5 T) pre- and 4-7 d post-TMLR. T1-weighted spin echo sequences were acquired ECG-triggered native and after injection of gadolinium. Qualitative analysis was performed on both native and contrast-enhanced images. Myocardial signal alterations and wall changes were evaluated. Qualitative and quantitative analyses of contrast-enhanced images were performed with regard of post-therapeutic perfusion differences. Analysis was based on contrast-to-noise (C/N) data obtained from operator defined "regions of interest". RESULTS: Visualization of laser-induced channels was not possible. Native scans obtained before and after TMLR revealed no significant change with regard to the qualitative analysis. Both qualitative and quantitative analyses demonstrated a posttherapeutic increase of C/N in both the left ventricular myocardium (64.4 pre-TMLR; 89.1 post-TMLR; p = 0.06) and the septum in the majority of cases. No significant difference between laser-treated left myocardium and untreated septum was observed (p > 0.05). DISCUSSION: Single myocardial laser channels could not be visualized with a 0.5-T MRI. However, visualization of increased myocardial contrast enhancement in laser-treated left ventricular myocardium was evident in the majority of cases on the basis of qualitative and quantitative analyses. CONCLUSIONS: The MRI technique used enabled a first, limited depiction of TMLR-induced myocardial changes. The clinical value and impact still have to be defined.

Aged↗

Dynamic MR defecography with a superconducting, open-configuration MR system.

PURPOSE: To evaluate dynamic magnetic resonance (MR) defecography performed with a superconducting, open-configuration system in diagnosis of defecation disorders. MATERIALS AND METHODS: Five healthy volunteers and 15 patients with defecation disorders were studied with MR defecography performed with a superconducting, open-configuration system; the patients also underwent fluoroscopic defecography. Before MR imaging, the rectum was filled with 300 mL of mashed potatoes mixed with 1.5 mL of gadopentetate dimeglumine. T1-weighted gradient-echo images were acquired every 2 seconds in the midsagittal plane with the patient at rest, at maximal contraction of the anal sphincter, during straining, and during defecation. RESULTS: MR defecography permitted analysis of the anorectal angle, anal canal, puborectal muscle, and descent of the pelvic floor. Owing to the high signal intensity of the intraluminal contrast material, the rectal walls were well demonstrated on the MR images, permitting visualization of intussusception and rectocele. Concomitant demonstration of structures surrounding the anorectal canal was helpful in assessment of spastic pelvic floor syndrome and descending perineum syndrome. MR defecography was superior to fluoroscopic defecography and allowed detection of all clinically relevant pathologic conditions except for one. CONCLUSION: Dynamic MR defecography is an attractive alternative for evaluation of defecation disorders.

Aged↗

Radio-frequency-induced thermoablation: monitoring with T1-weighted and proton-frequency-shift MR imaging in an interventional 0.5-T environment.

PURPOSE: To evaluate the feasibility and accuracy of monitoring radio-frequency (RF) ablation with an open-configuration, 0.5-T magnetic resonance (MR) imager. MATERIALS AND METHODS: Thirty-six in vivo RF ablation experiments were performed in porcine paravertebral muscle (n = 24) and liver (n = 12). A 90 degrees C tip temperature was applied for 3-9 minutes. MR images were acquired after continuous or during intermittent RF application. Temperature changes were monitored as signal intensity and proton-frequency-shift (PFS) alterations in two T1-weighted gradient-echo sequences. An update image was obtained every 2.5 seconds (20/10 [repetition time msec/echo time [TE] msec]) or every 5.0 seconds (40/20). A color-coded subtraction technique enhanced the signal intensity and PFS changes. Macroscopic coagulation size was compared with MR image lesion size. RESULTS: The RF application mode had no significant effect on coagulation size in muscle or liver (P > .05). Twenty-two of 24 coagulative lesions in muscle and nine of 12 in liver were demonstrated with the PFS technique. Accuracy of lesion size determination depended on TE (TE = 20 msec, r = .95; TE = 10 msec, r = .78 [P < .01]). The T1-weighted technique depicted only six of 24 muscle and three of 12 liver lesion ablations. In the lesions depicted, macroscopic size was significantly underestimated (P < .001). CONCLUSION: PFS MR monitoring of RF effects in liver and muscle is feasible and accurate. The PFS technique outperformed the T1-weighted technique.

Animals↗

Detection of mass lesions with MR colonography: preliminary report.

PURPOSE: To evaluate the performance of magnetic resonance (MR) colonography in the detection of colorectal mass lesions. MATERIALS AND METHODS: Twenty-three patients underwent MR colonography preceding colonoscopy. The colon was filled with a gadolinium-water mixture (1:100) with MR imaging guidance, and the patient was imaged prone and supine with a breath-hold three-dimensional spoiled gradient-recalled sequence. In addition, two-dimensional spoiled gradient-recalled images were acquired before and after intravenous administration of gadopentetate dimeglumine. Images were interactively analyzed on the basis of multiplanar reconstruction by two radiologists. For regions that were not conclusively assessable with multiplanar reconstruction, virtual intraluminal endoscopic images of the colon were reconstructed. MR findings were correlated with colonoscopic results. RESULTS: Two patients were excluded from the analysis. Findings in eight of 11 patients were correctly assessed as normal and in six of 10 as mass-positive. In the four patients with false-negative findings, one had two 8-mm polyps and the other three had polyps smaller than 5 mm. All nine mass lesions larger than 10 mm, as well as four of the 10 polyps ranging between 5 and 10 mm, were detected, but all polyps smaller than 5 mm were missed. In contrast to the polyps less than 5 mm, the four missed polyps (5-10 mm) could be identified retrospectively on virtual intraluminal endoscopic images. Contrast enhancement was documented in 13 polyps. CONCLUSION: Three-dimensional MR colonography provided virtual colonoscopic viewing and helped detection of colonic polyps.

Adult↗

Cdk2-dependent phosphorylation of p27 facilitates its Myc-induced release from cyclin E/cdk2 complexes.

Activation of Myc triggers a rapid induction of cyclin E/cdk2 kinase activity and degradation of p27. Overt degradation of p27 is preceded by a specific dissociation of p27 from cyclin E/cdk2, but not from cyclin D/cdk4 complexes. We now show that cyclin E/cdk2 phosphorylates p27 at a carboxy-terminal threonine residue (T187) in vitro; mutation of this residue to valine stabilises cyclin E/cdk2 complexes. This reaction is not significantly inhibited by high concentrations of p27, suggesting that cdk2 bound to p27 is catalytically active. In vivo, p27 bound to cyclins E and A, but not to D-type cyclins is phosphorylated. Myc-induced release of p27 from cdk2 requires cdk2 kinase activity and is delayed in a T187V mutant of p27. After induction of Myc, p27 phosphorylated at threonine 187 transiently accumulates in a non cdk2 bound form. Our data suggest a mechanism in which p27 is released from cyclin E/cdk2 upon phosphorylation; in Myc-transformed cells, release is efficient as phosphorylated p27 is transiently bound in a non-cdk2 containing complex and subsequently degraded.

Animals↗

Bronchiectasis in pediatric AIDS.

OBJECTIVES: There are several reports of the pulmonary findings in children with HIV disease; however, the occurrence of bronchiectasis rarely has been noted. We evaluated occurrence of bronchiectasis in a large group of children referred to us with AIDS pneumopathy. METHODS: From January 1984 to April 1996, 203 children with AIDS and respiratory problems were referred to the pediatric pulmonary division at Children's Medical Center of Brooklyn. Medical records for 164 of these children were available and retrospectively reviewed. RESULTS: Uncomplicated pneumonia was present in 75, 24 had recurrent pneumonia, and 18 had unresolved pneumonia; lymphocytic interstitial pneumonitis (LIP) was diagnosed in 47 patients, worsening with time in all patients. Bronchiectasis was observed in 26 patients (26/164, 15.8%), diagnosed by chest radiograph in 26 (26/26, 100%), confirmed by CT scan of chest in 10 (10/26, 38.4%), and by histology in three (3/26, 11.5%). Median age at time of diagnosis of bronchiectasis was 7.5 years (range, 1 to 16 years). Sixteen children with LIP developed bronchiectasis (16/47, 34.0%). Three patients with recurrent pneumonia (3/24, 12.5%) developed bronchiectasis. Five patients with unresolved pneumonia (5/18, 27.7%) developed bronchiectasis. One infant developed bronchiectasis after Pneumocystis carinii pneumonia; another child developed bronchiectasis after P. carinii and Mycobacterium tuberculosis pneumonia. The CD4+ T-cell counts measured within 6 months of diagnosis of bronchiectasis were available in 23/26 patients and, all were < 100 cells per cubic millimeter. CONCLUSION: We conclude, from our experience, that there is a significant occurrence of bronchiectasis in children with AIDS and pulmonary disease, especially in children developing LIP, recurrent pneumonia and unresolved pneumonia, and CD4+ T-cell counts < 100 cells per cubic millimeter.

AIDS-Related Opportunistic Infections↗