Topology of an intracellular transduction chain (phototropism of Phycomyces): 2. Mathematical model of pattern transduction.
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Adaptation, Physiological↗
Biomedical subjects
M Reinhardt
Publications and source records attributed to M Reinhardt.
Topology of an intracellular transduction chain (phototropism of Phycomyces): 1. Joint review of functional, temporal, and spatial aspects.
Two light-induced growth reactions in a unicellular cylindrical sporangiophore of Phycomyces blakesleeanus-vertical growth acceleration under symmetrical irradiation (photomecism) and directional growth under unilateral irradiation (phototropism)-share common input light perception as well as common output growth mechanism but have strongly divergent dynamics and other distinctive features. This divergence culminates in the phototropic paradoxes the main of which states that photomecism shows total adaptation, while phototropism does not adapt. The basis for this contradiction is that the phototropic transduction chain, unlike that of photomecism, faces a spatially non-uniform stimulus and processes a series of spatial patterns (light and absorption profiles, adaptation profile, etc.). The only way to resolve the paradoxes and correlate features of both responses within a single transduction chain is to assume non-local signal transduction, e.g. a cross-talk between different azimuthal locations within the cylindrical cell. On the other hand, to establish the presence of an appropriate cross-talk is equivalent of gaining insight into the topology of the transduction chain. This series of two papers contains a review reconsidering the entire field from this viewpoint (Paper 1) and a mathematical model of pattern transduction which unifies features of phototropism and resolves the paradoxes (Paper 2). At the same time, this is the first "proof of concept" for the "activity/pooling (a/p) networks"-a specific mathematical apparatus designed to analyse systemic properties and control in metabolic pathways.
Absorption↗
Nasal immunisation with Salmonella typhimurium producing rotavirus VP2 and VP6 antigens stimulates specific antibody response in serum and milk but fails to protect offspring.
Rotavirus specifically infects the small intestine of young infants resulting in severe diarrhoea. Mucosal antibody responses are required to cure the infection, and mucosal administration of rotavirus-like particles induces protective immunity without requiring a mucosal adjuvant such as cholera toxin. In addition, the rotavirus protein VP6 has been defined as a protective antigen in an adult mouse rotavirus infection model. Salmonella typhimurium is an epithelium-invasive bacterium that induces specific immune responses in mucosal tissues against itself and carried antigens. In this work, we investigated the capacity of a live recombinant S. typhimurium vaccine to stimulate antibody responses against rotavirus. We constructed an attenuated S. typhimurium strain simultaneously producing VP6 and VP2 rotavirus proteins in the cytoplasm. In contrast to expression in eukaryotic cells, VP6 and VP2 did not form virus-like particles in our bacterial system. After nasal administration of female mice, the live recombinant Salmonella were able to elicit an antibody response specific to both VP2 and VP6 in serum and milk. However, these antibodies failed to passively protect the offspring against rotavirus-induced diarrhoea.
Administration, Intranasal↗
2-(fluorine-18)fluoro-2-deoxy-D-glucose positron emission tomography in the detection and staging of malignant lymphoma. A bicenter trial.
BACKGROUND: The authors undertook a prospective evaluation of the clinical value of 2-fluoro [18-]-2-deoxyglucose positron emission tomography (FDG-PET) in the detection and staging of malignant lymphoma compared with computed tomography (CT) and bone marrow biopsy (BMB). METHODS: Fifty-two consecutive patients with untreated malignant lymphoma were evaluated prospectively in a bicenter study. FDG-PET, CT, and BMB were performed for investigating lymph node/extranodal manifestations and bone marrow infiltration. Thirty-three percnt of the discrepant results were verified by biopsy, magnetic resonance imaging, or clinical follow-up (range, 4-24 month). RESULTS: Altogether, 1297 anatomic regions (lymph nodes, organs, and bone marrow) were evaluated. FDG-PET and CT scans were compared by receiver operating characteristic (ROC) curve analysis. The area under the ROC curve were as follows: lymph nodes, 0.996 (PET) and 0.916 (CT); extranodal, 0.999 (PET) and 0.916 (CT); supradiaphragmatic, 0.996 (PET) and 0.905 (CT); and infradiaphragmatic, 0.999 (PET) and 0.952 (CT). In these analyses, FDG-PET was significantly superior to CT (P < 0.05), except in infradiaphragmatic regions, in which the two methods produced equivalent results. In detecting bone marrow infiltration, FDG-PET was superior to CT and was equivalent to BMB. In 4 of 52 patients (8%), FDG-PET led to an upstaging and a change of therapy. CONCLUSIONS: Noninvasive FDG-PET is very accurate in the staging of malignant lymphoma. Compared with standard staging modalities (CT and BMB), PET was significantly superior and led to changes in the therapy regimen for 8% of patients.
Adolescent↗
FDG-PET imaging for the staging and follow-up of small cell lung cancer.
The staging procedures for small cell lung cancer do not differ appreciably from those for other forms of lung cancer. For practical purposes, the TNM stages are usually collapsed into a simple binary classification: limited disease and extensive disease. This study was performed to answer the question of whether fluorine-18 labelled 2-deoxy-2-D-glucose positron emission tomography (FDG-PET) imaging permits appropriate work-up (including both primary and follow-up staging) of patients presenting with small cell lung cancer, as compared with currently recommended staging procedures. Thirty-six FDG-PET examinations were performed in 30 patients with histologically proven small cell lung cancer. Twenty-four patients were examined for primary staging while four were imaged for therapy follow-up only. Two patients underwent both primary staging and up to four examinations for therapy follow-up. Static PET imaging was performed according to a standard protocol. Image reconstruction was based on an ordered subset expectation maximization algorithm including post-injection segmented attenuation correction. Results of FDG-PET were compared with those of the sum of other staging procedures. Identical results from FDG-PET and the sum of the other staging procedures were obtained in 23 of 36 examinations (6x limited disease, 12x extensive disease, 5x no evidence of disease). In contrast to the results of conventional staging, FDG-PET indicated extensive disease resulting in an up-staging in seven patients. In one patient in whom there was no evidence for tumour on conventional investigations following treatment, FDG-PET was suggestive of residual viability of the primary tumour. Furthermore, discordant results were observed in five patients with respect to lung, bone, liver and adrenal gland findings, although in these cases the results did not affect staging as limited or extensive disease. Moreover, FDG-PET appeared to be more sensitive for the detection of metastatic mediastinal and hilar lymph nodes and bone metastases. Finally, all findings considered suspicious for tumour involvement on the other staging procedures were also detected by FDG-PET. It is concluded that FDG-PET has potential for use as a simplified staging tool for small cell lung cancer.
Adult↗
Psychological response and survival in breast cancer.
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Attitude to Health↗
Acoustic behaviour of current ultrasound contrast agents.
A general law gives the approximate change in signal level obtained in a particular imaging mode when a suitable contrast agent is added. It also shows that reduction of background signals is essential to overcome limitations found mainly in conventional (linear) ultrasound contrast imaging. Contrast agents contain stabilized microbubbles with very helpful non-linear properties. Acoustic methods for non-destructive and destructive testing of microbubbles are briefly discussed. In the main part, the linear and non-linear acoustic behaviour of various types of contrast agent are described. The latter is useful for new applications in diagnostic ultrasound.
Acoustics↗
First experiences in using a new ultrasound mode and ultrasound contrast agent in the diagnosis of blunt renal trauma: a feasibility study in an animal model.
RATIONALE AND OBJECTIVES: To evaluate the diagnostic value of the new ultrasound mode "wide-band harmonic" (WBH) using an ultrasound contrast agent in blunt renal trauma in an animal model. METHODS: A defined blunt renal trauma was induced in 10 rabbits according to published standards. Ultrasound (B-mode, color and power Doppler, WBH) was performed before and after trauma, with and without using a contrast agent (Levovist). Ultrasound features were compared with histologic findings. RESULTS: In 2 of the 10 rabbits, three focal renal intraparenchymal lesions with diameters ranging from 1.0 to 1.8 mm were found that could be identified only using WBH with contrast. Six of the 10 rabbits developed a subcapsular hematoma with a thickness of up to 1.5 mm, which was identified by conventional B-mode as well as WBH. Histologic workup confirmed these findings of intraparenchymal hematomas and did not reveal further lesions. CONCLUSIONS: Only 20% of the experimental subjects developed parenchymal lesions with diameters of 1.0 mm or larger. All these lesions were identified only using WBH. These results indicate the potential to use WBH plus contrast for the diagnosis of blunt renal trauma.
Animals↗
[Food allergies].
Clinical aspects of food allergies in infants and children are discussed together with diagnostic procedures in order to provide for practitioners a better understanding thus allowing a good management of pediatric patients with food-related disorders.
Bronchial Spasm↗
[Immunology summary or immunology in two hours].
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Allergy and Immunology↗
Cardiac uptake of [123I]MIBG separates Parkinson's disease from multiple system atrophy.
OBJECTIVE: To improve the differential diagnosis between patients with multiple system atrophy (MSA) and idiopathic PD (IPD) with autonomic failure. BACKGROUND: Some patients diagnosed with IPD are discovered to have alternative diseases such as MSA, despite the application of stringent diagnostic criteria. This differentiation is particularly difficult if patients with IPD also show symptoms of autonomic failure. In IPD, autonomic failure is caused by damage of the postganglionic part of the autonomic nervous system, whereas in MSA, degeneration of preganglionic and central autonomic neurons is revealed histopathologically. METHODS: Scintigraphy with [123I]metaiodobenzylguanidine (MIBG) enables the quantification of postganglionic sympathetic cardiac innervation. Fifteen patients with IPD and 5 patients with MSA underwent standard autonomic function tests and scintigraphy with MIBG. RESULTS: In all patients, cardiovascular testing showed evidence of autonomic failure of varying severity. In all patients with IPD, the heart-mediastinum (H/M) ratio of MIBG uptake was pathologically impaired, independent of duration and severity of autonomic and parkinsonian symptoms. All patients with MSA had a regular H/M ratio. Each patient could be assigned to the correct diagnostic group based on the results of the MIBG scintigraphy, even if the duration of the disease was only 2 years or less. CONCLUSIONS: This population assessment of the heart-mediastinum ratio of [123I]metaiodobenzylguanidine uptake showed a high sensitivity for the detection of autonomic involvement in patients with idiopathic IPD and also a high specificity for the discrimination between idiopathic PD and MSA.
3-Iodobenzylguanidine↗
In vitro comparison of the antigen-binding and stability properties of the various molecular forms of IgA antibodies assembled and produced in CHO cells.
The hallmark of a mucosal immune response is the production of antigen-specific secretory IgA (S-IgA) antibodies in external secretions. S-IgA consists of ten polypeptides produced in two different cell lineages. The heavy and light chains in plasma cells assemble into IgA, which on association with J chain become polymerized, whereas secretory component (SC) is added during transport across the epithelium. Recombinant chimeric mouse-human monomeric, dimeric, and S-IgA antibodies have been produced in a single CHO cell sequentially transfected with expression vectors carrying three independent selective markers for chimeric heavy and light chains, human J chain, and human SC, respectively. Biochemical characterization of the various molecular forms indicates that the assembly of the various polypeptides resulted in species of the expected size and covalence. All chimeric IgA antibodies retained the antigen-binding capacity of the parent mouse IgA antibody. The resistance of S-IgA to protease-rich intestinal washes was enhanced when compared with dimeric IgA lacking associated SC. Up to 20 micrograms of recombinant S-IgA per 1 x 10(6) cells were recovered in 24 h with the best producing clones. We conclude that CHO cells programmed de novo with four different genetic elements can assemble functional chimeric S-IgA.
Animals↗
Wideband harmonic imaging: a novel contrast ultrasound imaging technique.
A novel ultrasonic imaging method, wideband harmonic imaging, for nonlinear imaging of microbubble contrast agents is evaluated. In wideband harmonic mode, two pulses of alternate phase are send out. The image is then processed from the sum of both pulses, resulting in an image of nonlinear scatterers such as microbubbles. A prototype ultrasound system, Siemens Elegra, was evaluated with in vitro investigations and animal trials, using conventional, harmonic and wideband harmonic settings with the galactose based ultrasound contrast agent Levovist. Wideband harmonic imaging offers superior sensitivity for ultrasound contrast agents compared to conventional imaging and harmonic imaging. At low transmit power settings (MI 0. 1-0.5) the nonlinear response is already sufficient to generate a image of the blood pool distribution of Levovist in the rabbit kidney including the microvasculature, with clear delineation of vessels and perfused parenchyma. At high transmit amplitudes, nonlinear tissue response reduced the apparent image contrast between contrast agent and tissue. The results suggest that wideband harmonic imaging is currently the most sensitive contrast imaging technique, maintaining highest spatial resolution. This may add to image quality and offer new clinical potential for the use of ultrasound contrast agents such as Levovist.
Animals↗
Bone marrow scintigraphy using technetium-99m antigranulocyte antibody in malignant lymphomas.
BACKGROUND: The purpose of this study was to elucidate the clinical reliability of immunoscintigraphy (IS) to detect infiltration of the bone marrow in patients with malignant lymphoma. PATIENTS AND METHODS: Whole body IS was performed in 103 patients with Hodgkin's disease (HD) or non-Hodgkin's lymphoma (NHL) using Tc-99m labelled anti-NCA-95 which allows visualization of the granulopoietic bone marrow. Of these, 52% were studied prior to any therapy. Findings were compared to posterior iliac crest biopsy as well as MRI and/or follow-up examination. Criteria of marrow infiltration were a positive biopsy, positive follow-up, or positive results of MRI. RESULTS: Comparison of IS and biospy revealed concordant findings in 69 and discordant findings in 34 of 103 patients. Of the 34 patients with discordant results, IS showed lesions suspicious of bone marrow infiltration in 29 patients despite normal biopsy findings. When follow-up and additional examinations were taken into consideration, 10 patients remained with probably false positive and five with false negative IS findings. IS proved to be highly sensitive and specific in patients with HD (100% and 84%, respectively) and high-grade NHL (93% and 84%, respectively). Moderate sensitivity (60%) was found in low-grade NHL. This was possibly due to false negative IS in three to five patients with chemotherapy in contrast to one of five false negative results in patients without chemotherapy. CONCLUSION: Bone marrow scintigraphy using antigranulocyte antibodies is highly sensitive in HD and high-grade NHL. Positive findings in IS subsequent to a negative biopsy should be followed by guided re-biopsy or MRI.
Adolescent↗
Staging of pelvic lymph nodes in neoplasms of the bladder and prostate by positron emission tomography with 2-[(18)F]-2-deoxy-D-glucose.
OBJECTIVES: The aim of this study was to evaluate whether pelvic lymph node metastases in patients with neoplasms of the bladder or prostate can be detected applying positron emission tomography with 2-[(18)F]-2-deoxy-D-glucose (FDG-PET). METHODS: Eight patients with bladder cancer and 17 patients with prostate cancer were examined with FDG-PET before pelvic lymph node dissection. Results of PET were then compared to histology of pelvic lymph nodes obtained at surgery. RESULTS: Lymph node metastases were detected by histopathological examination in 3 patients with bladder cancer and in 6 patients with prostate cancer. At the sites with histologically proven metastases, increased FDG uptake suspicious of metastatic disease was found in 2/3 and 4/6 patients, respectively. The smallest detected metastasis was a micrometastasis with a diameter of 0.9 cm. In 3 additional patients who all had histopathologically proven micrometastases ( </=0.5 cm), FDG uptake was within the normal range. No false-positive results were obtained. CONCLUSIONS: These results suggest that FDG-PET may be a valuable diagnostic tool in the staging of pelvic lymph nodes in bladder and prostate cancer.
Aged↗
Photopenic lesions in bone marrow scintigraphy using technetium-99m labeled antigranulocyte antibody without known tumour.
AIM: The purpose of this study was to elucidate the frequency of photopenic lesions in patients without known tumour disease by using bone marrow scintigraphy with Tc-99m labeled anti-NCA-95. METHODS: Whole body immunoscintigraphy (IS) was performed in 141 consecutive patients with fever of unknown origin. The age ranged between 20 and 88 years with a mean age of 57 years. None of the patients had known tumour disease. Scans were evaluated with respect to photopenic lesions and to bone marrow distribution. RESULTS: IS showed bone marrow defects in the axial skeleton in 16 patients (11%). With the help of the typical scintigraphic defect pattern, the cause of the lesions was clearly identified as degenerative changes in four patients and in one patient as due to prior sternotomy. In the remaining 11 patients the origin of the defects became evident when the case history or additional imaging was consulted. The mean age of these 16 patients was 69 years ranging from 50 to 88 years. There was an age-related frequency of defects. 10% of the patients from 50 to 59 years showed defects, 60-69 years 9%, 70-79 years 30%, and 33% of the patients from 80 to 89 years had defects. IS was not hampered by tracer uptake to liver or spleen in 93 patients. Left caudal ribs were obscured in 48 patients with intense tracer uptake to the spleen. No or markedly reduced tracer uptake was found in caput humeri and caput femori in 94 and 82 patients, respectively. Patchy tracer uptake to the bone marrow of the limbs was seen in 13/62 patients showing marrow expansion in the lower limbs and 14/55 with marrow expansion in the upper limbs. The patchy pattern was asymmetric in 12 of these patients. CONCLUSION: The results of the present study reveal that using Tc-99m NCA-95, photopenic lesions of the bone marrow are rarely seen in patients without known malignant disease. The occurrence of benign lesions is age-related. The benign cause of the lesion was obvious from location and pattern of the lesion in about 30% of the cases. Evaluation of lesions in the upper and lower limbs may be hindered due to physiological variation of marrow distribution. Nevertheless, IS appears to be well-suited for the detection and localization of bone marrow metastases.
Adult↗
Quantification of glucose transport and phosphorylation in human skeletal muscle using FDG PET.
UNLABELLED: PET with 2-[18F]-fluoro-2-deoxy-D-glucose (FDG) is used for quantifying glucose metabolism in brain and myocardium in vivo. We developed and validated a similar procedure for the quantification of the two initial steps of glucose metabolism in skeletal muscle in vivo. METHODS: The measurement protocol was first optimized by computer simulations. In addition to the accuracy in sampling plasma input and tissue time-activity curves, precise determination of the fractional blood volume, that is, the extracellular tissue volume fraction, plays a key role in correctness of the determined model constants. The optimized protocol was subsequently used to estimate transmembrane muscular glucose transport and hexokinase activity in six human subjects with normal or altered glucose utilization. PET was performed during the steady state of an euglycemic hyperinsulinemic clamp. RESULTS: A three-compartment model provides a better description of the experimental data than a two- or four-compartment model. Glucose clearance from the extracellular compartment into the skeletal muscle cell (K1) ranges from 0.024 to 0.093 mL/g/min. The intracellular glucose phosphorylation rate (k3) varies between 0.030 and 0.142 min(-1). The regional muscular glucose utilization, as calculated from the determined model parameters, lies between 10.7 and 83.3 micromol/kg/min and correlates with the whole-body glucose utilization as independently determined (R2 = 0.83; P < or = 0.01). CONCLUSION: We demonstrate by computer simulations that a three-compartment model can be used to characterize the first two steps of glucose metabolism in skeletal muscle. An optimized measurement protocol is developed and applied to experimental data. This experimental approach should be appropriate to test whether glucose transport or hexokinase activity is altered in disorders of muscular glucose utilization.
Adult↗