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Biomedical subjects

J Lorenz

Publications and source records attributed to J Lorenz.

At least 19 recordsLinked to original sources

Rescue of cardiac alpha-actin-deficient mice by enteric smooth muscle gamma-actin.

The muscle actins in higher vertebrates display highly conserved amino acid sequences, yet they show distinct expression patterns. Thus, cardiac alpha-actin, skeletal alpha-actin, vascular smooth muscle alpha-actin, and enteric smooth muscle gamma-actin comprise the major actins in their respective tissues. To assess the functional and developmental significance of cardiac alpha-actin, the murine (129/SvJ) cardiac alpha-actin gene was disrupted by homologous recombination. The majority ( approximately 56%) of the mice lacking cardiac alpha-actin do not survive to term, and the remainder generally die within 2 weeks of birth. Increased expression of vascular smooth muscle and skeletal alpha-actins is observed in the hearts of newborn homozygous mutants and also heterozygotes but apparently is insufficient to maintain myofibrillar integrity in the homozygous mutants. Mice lacking cardiac alpha-actin can be rescued to adulthood by the ectopic expression of enteric smooth muscle gamma-actin using the cardiac alpha-myosin heavy chain promoter. However, the hearts of such rescued cardiac alpha-actin-deficient mice are extremely hypodynamic, considerably enlarged, and hypertrophied. Furthermore, the transgenically expressed enteric smooth muscle gamma-actin reduces cardiac contractility in wild-type and heterozygous mice. These results demonstrate that alterations in actin composition in the fetal and adult heart are associated with severe structural and functional perturbations.

Actins

Induction of accessory cell function of human alveolar macrophages by inhalation of human natural interleukin-2.

Accessory function allows antigen-presenting cells to produce sufficient secondary signals for optimum T cell proliferation and interleukin-2 (IL-2) production. Alveolar macrophages are inferior accessory cells compared to monocytes (PBM). We report here that the accessory index (AI) of alveolar macrophages and PBM of patients with lung metastases of solid tumors treated with inhalations of human natural IL-2 (hnIL-2) increased following its administration (P<0.005). The accessory index was significantly elevated from baseline values after 2 weeks of inhalation of 300,000 IU hnIL-2/day (8.2 +/- 10.2 compared to 1.1 +/- 1; P<0.001). The inhalation of 150,000 IU also induced increases in the index (AI = 2.3 +/- 1.9), however, without reaching statistical significance. In addition at 300000 IU IL-2/day a significant increase in the accessory index was observed for PBM (4 +/- 2.5; P<0.05). The indices of PBM and alveolar macrophages prior to inhalation showed a significant negative correlation with the age of the patients (r(s) = -0.5; r(s) = -0.8, respectively; P<0.03 for all comparisons). Our data demonstrate that the inhalational application of hnIL-2 enhances the accessory function of alveolar macrophages and, to lesser extent, the accessory index of PBM, indicating the occurrence of pharmacological immunostimulation.

Administration, Inhalation

Middle and long latency somatosensory evoked potentials after painful laser stimulation in patients with fibromyalgia syndrome.

Ten female patients with fibromyalgia syndrome (FS) were investigated with laser evoked potentials (LEPs) after hand stimulations and compared with 10 female pain-free and age-matched control patients. FS patients exhibited significantly lower heat pain thresholds than controls (P < 0.05) and had higher amplitudes of LEP components N170 (P < 0.01) and P390 (P < 0.05) in response to intensities of 20 W (beam diameter 5 mm, duration 20 msec, wavelength 10.6 microns). N170 additionally appeared with a broader distribution over bilateral central, vertex and fronto-central leads which contrasted to the control group and studies in healthy subjects where N170 was much more restricted to central and midtemporal positions contralateral to the stimulated hand. Auditory stimuli interspersed between laser impulses that served to announce subjects to rate the perceived pain elicited auditory evoked potentials that were not different between groups indicating no differences of general vigilance level to account for observed LEP effects. P390 amplitude enhancement might indicate greater attention and cognitive processing of nociceptive stimuli in FS subjects. Effects upon N170 rather point to exogenous factors like peripheral and spinal sensitization or reduced cortical or subcortical inhibition of nociception.

Adult

Expression of cell adhesion molecules in lung cancer cell lines.

Cell adhesion mechanisms are among the basic aspects in organism development. Adhesion molecules are involved in the building of complex structures and of association of the tissue. They also mediate as substratum adhesion molecules and are involved in the building of the scaffold. The process of tumor growth and metastasis is a complex cascade of events (FIDLER 1989). For many of these steps the tumor cells must be able to change their degree of adherence. Tumor progression and metastatic dissemination are tightly linked with the ability of the tumor cells to interact with other cells and with the extracellular matrix. The first step of metastasis is the active migration of tumor cells into the surrounding tissue.

Antigens, CD

Performance and brain electrical activity during prolonged confinement.

A subset of the AGARD-STRES battery including memory search, unstable tracking, and a combination of both tasks (dual-task), was applied repeatedly to the four chamber crew members before, during, and after the 60-day isolation period of EXEMSI. Five ground control group members served as a control group. A subjective state questionnaire was also included. The results were subjected to a quantitative single-subject analysis. Electroencephalograms (EEG) were recorded to permit correlation of changes in task performance with changes in the physiological state. Evaluation of the EEG focused on spectral parameters of spontaneous EEG waves. No physiological data were collected from the control group. Significant decrements in tracking ability were observed in the chamber crew. The time course of these effects followed a triphasic pattern with initial deterioration, intermediate recovery to pre-isolation baseline scores after the first half of the isolation period, and a second deterioration towards the end. None of the control group subjects displayed such an effect. Memory search (speed and accuracy) was only occasionally impaired during isolation, but the control group displayed a similar pattern of changes. It is suggested that a state of decreased alertness causes tracking deterioration, which leads to a reduced efficiency of sustained cue utilization. The assumption of low alertness was further substantiated by higher fatigue ratings by the chamber crew compared to those of the control group. Analysis of the continuous EEG recordings revealed that only two subjects produced reliable alpha wave activity (8-12 Hz) over Pz and, to a much smaller extent, Fz-theta wave activity (5-7 Hz) during task performance. In both subjects Pz-alpha power decreased consistently under task conditions involving single-task and dual-task tracking. Fz-theta activity was increased more by single-task and dual-task memory search than by single-task tracking. The alpha attenuation appears to be associated with an increasing demand on perceptual cue utilization required by the tracking performance. In one subject marked attenuation of alpha power occurred during the first half of the confinement period, where he also scored the highest fatigue ratings. A striking increase in fronto-central theta activity was observed in the same subject after six weeks of isolation. The change was associated with an efficient rather than a degraded task performance, and a high rating of the item "concentrated" and a low rating of the item "fatigued." This finding supports the hypothesis that the activation state associated with increased fronto-central theta activity accompanies efficient performance of demanding mental tasks. The usefulness of standardized laboratory tasks as monitoring instruments is demonstrated by the direct comparability with results of studies obtained from other relevant research applications using the same tasks. The feasibility of a self-administered integrated psychophysiological assessment of the individual state was illustrated by the nearly complete collection of data. The large number of individual data collected over the entire period permitted application of quantitative single-subject analysis, allowing reliable determination of changes in the individual state in the course of time. It thus appears that this assessment technique can be adapted for in-flight monitoring of astronauts during prolonged spaceflights. Parallel EEG recording can provide relevant supplementary information for diagnosing the individual activation state associated with task performance. The existence of large individual differences in the generation of task-sensitive EEG rhythms forms an important issue for further studies.

Adult

[Stent implantation as a palliative therapeutic measure in stenosing tumors of central airways].

PURPOSE: Stent implantation was used to treat patient with malignant tracheobronchial obstructions to determine the effectiveness in producing symptomatic palliation. METHODS: 18 patients (15 men and three women; median age 57 years) with malignant tracheobronchial stenosis were treated by application of metal stents (15 Palmaz-, 10 Gianturco-, 4 Wallstents). The indication for stent implantation was given in 13 patients by clinically significant dyspnea, besides in 5 patients by therapy resistant postobstructive pneumonia. RESULTS: In 17 patients correct positioning of the stents was achieved and the symptoms completely disappeared until tumor related death. Median survival was 137 days (min. 10 days to max. 322 days). In one patient symptoms recurred three months after stent implantation. CONCLUSION: The application of metal stents in patient with malignant tracheobronchial obstruction appears to be a useful palliation procedure. The treatment was well tolerated and very effective.

Adult

[Phantom study of optimization of spiral-CT and 3D reconstruction of the tracheobronchial system].

PURPOSE: To optimise three-dimensional spiral CT of the tracheobronchial tree using adequate acquisition and reconstruction parameters for spiral CT of the chest. MATERIAL AND METHODS: Qualitative and quantitative assessment of different 3 D reconstructions of two test objects of the tracheobronchial tree depending on section thickness, reconstruction interval, pitch, and reconstruction algorithm used in spiral CT (Siemens, Somatom plus S) of the chest. The frequency of volume and stairstep artifacts was evaluated. The 3 D reconstructions were generated using a seeded VOI-technique (Allegro, ISG). RESULTS: Reduction of artifacts was achieved by decreasing section thickness. Increasing overlap of source images, lowering the pitch factor, and application of the reconstruction algorithm "slim". Section thickness was the single most important factor which was mainly responsible for the occurrence of volume artifacts. Stairstep artifacts were primarily influenced by the reconstruction interval. CONCLUSION: Spiral CT with a section thickness > 4 mm is not adequate for 3 D reconstructions of the tracheobronchial tree. Overlapping source images with a pitch of 1 and the reconstruction algorithm "slim" can be recommended to reduce artifacts.

Algorithms

Recovery from brain-stem lesions involving the nociceptive pathways: comparison of clinical findings with laser-evoked potentials.

Dissociated sensory impairment in brain-stem disorders suggests a lateral lesion involving the spinothalamic tract. Evoked potential studies of the somatosensory system with standard electrical stimulation (SEP) generally fail to establish objective correlates of such sensory deficits, because electrical stimuli predominantly activate large myelinated fibers that project into the medial lemniscal system. In contrast, laser-evoked potentials (LEPs), in response to brief radiant heat pulses, stimulate nociceptive afferents of the superficial skin and allow evaluation of thin fiber and spinothalamic tract function. We describe the recovery of deficits in pain sensitivity in five patients with isolated lateral brain-stem lesions that could be successfully monitored by LEP recordings in the acute stage and after intervals ranging from 7 months to 4 years. Upon first examination, LEPs were abnormal on the affected body side in all five cases of lateral medullary syndrome, irrespective of whether the etiology was vascular or inflammatory. The degree of recovery of pain sensitivity upon reexamination was reflected by the extent of normalization of the LEP. A control patient with vascular pontine lacunar stroke had normal LEPs on both sides, suggesting preserved spinothalamic conduction. The peak-to-peak amplitude of the main LEP component (N250-P400) correlated significantly with clinical pain sensitivity scored by standardized sensory testing (r = 0.76, p < 0.01). In contrast, early and late SEPs, after standard electrical median or tibial nerve stimulation, were normal in all patients, consistent with their intact mechanosensitivity. In conclusion, LEP studies allow the status of nociceptive function to be objectively and reliably documented on repeated examinations and therefore provide a useful supplement to multimodal sensory assessment in brain-stem disorders.

Adult

Sensory deficits of a nerve root lesion can be objectively documented by somatosensory evoked potentials elicited by painful infrared laser stimulations: a case study.

Somatosensory evoked potentials (SEPs) in response to painful laser stimuli were measured in a patient with a unilateral sensory deficit due to radiculopathy at cervical levels C7 and C8. Laser evoked potentials (LEPs) were compared with SEPs using standard electrical stimulation of median and ulnar nerves at the wrist and mechanical stimulation of the fingertips by means of a mechanical stimulator. Early and late ulnar and median nerve SEPs were normal. Mechanical stimulation resulted in w shaped early SEPs from all five fingertips with some degree of abnormality at the fourth and fifth digits of the affected hand. Late LEPs were completely absent for stimulations at affected dermatomes and normal in the unaffected control dermatomes. The border between skin areas with normal or absent LEPs was very sharp and fitted the dermatomes of intact C6 and damaged C7 and C8 nerve roots. It is suggested that pain dermatomes are narrower than tactile dermatomes because thin fibres of the nociceptive system, activated by laser stimuli, probably do not overlap between adjacent spinal segments to the same extent as thick fibres of the mechanoreceptive system, activated by standard electrical or mechanical stimulation.

Aged

Three-dimensional helical CT of the tracheobronchial tree: evaluation of imaging protocols and assessment of suspected stenoses with bronchoscopic correlation.

OBJECTIVE: To assess the accuracy of three-dimensional (3D) helical CT of normal airways, we evaluated different imaging protocols in test objects and patients. The clinical value of 3D helical CT was composed with bronchoscopy in patients with suspected stenoses, especially before and after endobronchial procedures. SUBJECTS AND METHODS: Solid test objects--one of central airways and one of peripheral airways--were scanned and assessed for volume defects and stairstep artifacts. Fifty helical studies were performed in 36 patients. We evaluated these images for visualization of segmental bronchi; frequency of artifacts; and presence, localization, and degree of stenoses. Bronchoscopic correlation was available for 40 CT examinations. Follow-up 3D helical CT after endobronchial procedures was performed in nine patients. RESULTS: In test objects, thin sections reduced volume artifacts. Overlapping sections mainly diminished stairstep artifacts. In vivo, overlapping sections were superior to contiguous sections for good visualization of the origin (96% versus 89%, p < .01) and of the course (75% versus 54%, p < .001) of segmental bronchi. Three-dimensional helical CT allowed us to assess accurately 36 of 36 central stenoses that were seen on bronchoscopy; however, on 3D helical CT, we missed two of three segmental stenoses. At bronchoscopy, 18 stenoses could not be passed, whereas 3D helical CT provided details for possible endobronchial procedures: length of stenosis, patency (12/18), and spatial orientation of distal bronchi. Follow-up 3D helical CT documented the efficacy of endobronchial treatment. CONCLUSION: Three-dimensional helical CT based on thin overlapping sections accurately visualized the normal airways down to the origin of the segmental bronchi and central stenoses. When it complements bronchoscopy, 3D helical CT allows visualization beyond stenoses, supports planning of endobronchial procedures, and may even substitute for bronchoscopy after endobronchial procedures.

Adult

Pruritus circumscriptus sine materia: a sequel of postzosteric neuralgia. Evaluation by quantitative psychophysical examination and laser-evoked potentials.

A case of circumscribed pruritus existing since 1 year on clinically uninvolved skin is reported, in which careful history revealed a 5-year previous episode of herpes zoster in the same dermatome. Impairment of cutaneous sensitivity was evaluated by use of a quantitative psychophysical examination and laser-evoked cortical potentials (LEP).

Aged

Focal hepatic vein stenoses in diffuse liver disease.

To determine the frequency of focal hepatic vein stenosis in diffuse liver disease and to study the relationship of stenosis to abnormal hepatic venous Doppler waveforms, 92 patients being evaluated for liver transplantation or transjugular intrahepatic portosystemic shunt were prospectively studied with color flow and pulsed Doppler sonography for the presence of focal hepatic vein stenoses and waveform abnormalities. Thirty-six patients had no focal stenoses with normal curves, 26 of 38 patients with Bolondi type I curves had focal stenoses, and 10 of 18 patients with damped type II curves had focal stenoses. Damped hepatic venous velocity curves associated with liver disease probably are caused by increased resistance in the hepatic venous circulation produced by focal stenoses.

Constriction, Pathologic

[Upper inflow congestion as initial manifestation of idiopathic mediastinal fibrosis].

In about 90% of superior vena caval obstructions the cause is a neoplasm, generally a carcinoma of the right upper lobe. Fewer than 5 percent are due to inflammatory disease of the mediastinum. A case of idiopathic, fibrosing mediastinitis with occlusion of the superior vena cava is described. The clinical symptoms, radiographic finding, diagnostic and therapeutic aspects are discussed.

Adult

[Stent implantation for the palliative therapy of upper inflow obstruction in bronchial carcinoma].

AIM OF STUDY: To analyse results obtained in the palliative treatment of obstruction of the upper inflow veins by stent implantation in patients with bronchial carcinoma. PATIENTS AND METHODS: Stents were implanted in 14 patients with upper venous obstruction due to bronchial carcinoma (three women, eleven men: mean age 64 [48-74] years), 4 of the superior vena cava (SVC), 6 of the SVC and brachiocephalic vein, 4 of the SVC and subclavian vein. To prevent thromboembolic phenomena all patients received heparin in therapeutic doses for 1-3 days from the time of stents implantation. RESULTS: Treatment was successful (regression of the clinical signs) in 12 of the 14 patients. Six patients died, without recurrence of the clinical signs, an average of 141 (10-420) days after the procedure. Mean survival time of the six patients who remained without symptoms was 3 months (longest interval 9 months). In one patient thrombotic occlusion of the SVC occurred 6 days after stent implantation. However, local thrombolysis successfully re-opened the vessel. Renewed upper vein obstruction occurred in two patients during follow-up. None of the stent filaments fractured and there was no stent dislocation. CONCLUSION: With a success rate of 86% stent implantation proved to be a sparing procedure in the palliative treatment of upper inflow vein obstruction, especially in patients with extensive malignant disease.

Aged

Identification of 4-(N,N-dipropylamino)benzaldehyde as a potent, reversible inhibitor of mouse and human class I aldehyde dehydrogenase.

As the physiologic roles for the different classes of aldehyde dehydrogenase (ALDH) enzymes are elucidated, the identification of specific, reversible inhibitors becomes of great pharmacologic interest. Previous structure-function studies identified dialkylamino substituted benzaldehyde compounds as a novel class of reversible inhibitors of class I ALDH. To examine further structural requirements for inhibition, we tested a series of 4-(N,N-dialkylamino)benzaldehyde analogs as inhibitors of propanal oxidation by mouse liver and human erythrocyte class I ALDH. 4-(N,N-dipropylamino)benzaldehyde (DPAB) was identified as the most potent, reversible inhibitor of propanal oxidation by class I ALDH in spectrophotometric enzyme assays. In kinetic studies, DPAB showed mixed-type inhibition with respect to the aldehyde substrates propanal, phenylacetaldehyde, benzaldehyde, and aldophosphamide. DPAB exhibited uncompetitive inhibition with respect to the cofactor NAD. Inhibition constants (Ki) for DPAB, estimated from Dixon plots, were 10 nM (propanal) and 77 nM (phenylacetaldehyde) for mouse ALDH and 3 nM (propanal) and 70 nM (phenylacetaldehyde) for human ALDH. These Ki values are 100-fold lower than those reported for class I specific inhibitors. At low (< 1 microM) DPAB concentrations, inhibition of propanal and aldophosphamide oxidation was > 75%, whereas inhibition of benzaldehyde (32%) and phenylacetaldehyde (19%) oxidation was reduced markedly. These results indicate that DPAB exhibits potent, reversible inhibition of mouse and human class I ALDH. The degree of inhibition was highly dependent on the structure of the aldehyde substrate.

Acetaldehyde

[Stent implantation as a palliative therapeutic measure in tumor-induced stenoses of the large veins of the body].

PURPOSE: Self-expandable metallic stents were used to treat patients with malignant venous obstructions to determine their effectiveness in producing symptomatic palliation. METHODS: 20 patients with a total of 28 tumour-induced obstructions of the superior vena cava (n = 13), the inferior vena cava (n = 4), the subclavian (n = 4), the innominate (n = 5) and the iliac veins (n = 2) were treated with self-expandable metallic stents. 38 Gianturco stents and 21 Wallstents were applied. Patients were heparinised during the procedure and up to three days afterwards. RESULTS: In all patients correct positioning of the stents was achieved. In 16 patients stent placement resulted in relief of their symptoms. In 8 patients the symptoms completely disappeared without recurrence until death as a result of tumour progression. The follow-up ranged from 10 days to 14 months. In 8 still living patients no re-obstruction occurred (follow-up average three months). In one patient thrombotic stent occlusion occurred 6 days after the procedure; the v. cava superior was reopened again by local urokinase therapy. Three patients finally developed re-occlusion due to tumour progression. In one patient stent placement was complicated by migration of the Gianturco stent one day after stent implantation and reocclusion of the subclavian vein. CONCLUSION: The application of self-expandable metallic stents in patients with malignant venous obstruction is a useful palliative therapy.

Adult

Liver cirrhosis associated with heterozygous alpha-1-antitrypsin deficiency type Pi MS and autoimmune features.

Patients with homozygous protease inhibitor (Pi) type ZZ or a few rare M-like types may develop liver cirrhosis due to intracellular storage of alpha-antitrypsin (AAT), whereas some patients with heterozygous Pi MZ or SZ normally present with transient abnormal liver function tests in childhood. We report a 42-year-old obese patient who developed liver cirrhosis in association with heterozygous Pi MS (AAT) deficiency. Immunohistological and electron microscope examination showed storage of AAT in the hepatocytes. Interestingly, autoimmune features in this patient suggest that abnormal immune responses may contribute to the pathology of chronic liver disease.

Adult