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BACKGROUND: The prognosis for patients with squamous cell carcinoma of the head and neck (SCCHN) has remained poor during the last decades, emphasizing the need for new treatment modalities. Consequently, the objective of our study was to evaluate the feasibility and efficacy of cytokine-mediated gene therapy in SCCHN in vitro. MATERIALS AND METHODS/RESULTS: The SCCHN cell line PCI-1 was transduced by lipofection with a plasmid encoding the human granulocytemacrophage colony-stimulating factor (GM-CSF). Transfection of PCI-1 resulted in the production of significant amounts of GM-CSF as tested by ELISA. Enhanced proliferation of a GM-CSF sensitive cell line, TF-1, after incubation with supernatants of GM-CSF-transduced tumor cells demonstrated the release of biological active GM-CSF from these PCI-1 cells. In addition, GM-CSF-secreting PCI-1 cells enhanced antitumor cytotoxicity of allogeneic peripheral blood mononuclear cells, as tested in 24h-MTT-cytotoxicity assays. CONCLUSIONS: Our data demonstrate the feasibility and efficacy of GM-CSF-mediated stimulation of the antitumor immune response against SCCHN in vitro and may help to define new strategies in the treatment of this malignancy.

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Cervically induced eye movements consist of a nystagmus and a deviation of the mean eye position (shift). They show in relation to different neck torsion velocities maximum reactions at slow velocities. The clinical significance of these cervico-ocular reactions is discussed controversially. Therefore we investigated 40 healthy subjects without any neurootological findings, who, in addition, underwent a manual examination. The neck torsion test was performed automatically with quantifiable stimulus parameters and a complete head fixation by means of individual dental casts. It could be shown that at a constant chair velocity of 5 degrees/s every healthy subject exhibits cervical nystagmus and/or shift deviations. In comparison a group of 30 patients with an upper cervical spine syndrome also showed similar cervico-ocular reactions without significant difference. It can be concluded that a muscle hypertonus in the deep neck region does not lead to pathological, cervically induced eye movements and that the cervical nystagmus itself is not a pathognomonic sign for cervical, proprioceptive vertigo.

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In the glottal area, a series of transversal sections was recorded by means of a nuclear magnetic resonance tomograph using the technique of fast FLASH recording. During the record, the subject uttered the vowel [a:] with 180 Hz and 80 dB(A). The flip angle (35 degrees C) was chosen so as to get maximum contrast in the tissue tomogram due to a temperature shift. The tissue temperature was evaluated by the measurement of the dependence of the relaxation time on the temperature in a gelatinized and doped test solution which was similar in relaxation times to the tissue. In the vocal folds, the temperature increased by about 4 degrees C after prolonged phonation (20 x 20 s). The importance of this technique and the result is discussed with reference to the phonatory function of the larynx.

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Comparative phosphorus-31 magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) of 15 patients with superficial masses such as sarcoma, carcinoma, lymphoma, adenoma, and tuberculosis revealed significant increased concentrations of phosphomonoester, phosphodiester, and inorganic phosphorus in the lesion, whereas the concentration of the phosphocreatine was lower in comparison to muscle tissue. In nearly all masses, pH showed a slight alkaline shift. Existence of necrotic regions detected by MRI was marked by an increase of inorganic phosphorous in the spectra. Tumor growth was characterized by raised concentrations of phosphomonoester. Follow-up studies in a case of lymphoma showed a six-fold decrease of the tumor, while the spectra indicated a gradual transition of tumor values to muscle values. A follow-up study during irradiation of a squamous cell carcinoma revealed a considerable decrease of inorganic phosphate and a subsequent increase of phosphodiester.

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Simultaneous 31P-MR spectroscopy (MRS) and MR imaging (MRI) of 10 patients suffering from superficial tumours like carcinoma, lymphoma and adenoma, revealed significantly enhanced concentrations of phosphomonoester, phosphodiester and inorganic phosphorus in the tumour, whereas the concentration of phosphocreatine was lower in comparison to muscle tissue. In all tumours the pH showed a slight alkaline shift. The existing of necrotic regions detected by MRI was accompanied by an increase of inorganic phosphorus in the spectra. A follow-up study of a patient with a lymphoma during chemotherapy showed a tumour regression, whereas the spectra indicated a continuous approach of tumour values to the muscle values.

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Experiments with stimulation or denervation of cervical dorsal roots in animals have shown that input of the deep neck region is important for orientation, upright posture and the control of eye movements. Muscle spindles seem to play a dominant role as receptors for neck movements. Different ascending pathways project to the central nervous system and the signals interact with visual and vestibular stimuli. Cervical afferences provide a stabilization of the trunk during head movements because neck reflexes cancel labyrinthine reflexes. Posturographic measurements with head extension manoeuvres however did not turn out to be helpful in dizzy patients. Cervically induced eye movements are part of the complex head-eye coordination. The characteristics of cervico-ocular reactions are described. They show in relation to different neck torsion velocities a tuning curve with maximum reactions at slow velocities. Therefore the velocity of trunk rotation is, among others, an important factor when stimulating cervical afferences. The results from literature as well as own experiments show that there exists no method as yet that could yield positive evidence of cervical dizziness.

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Rotation of the trunk with a fixed head causes isolated stimulation of cervical afferent input. Eleven patients with marked cervico-ocular reactions (COR) were selected. A neck torsion test (NTT) was performed with the help of a special apparatus. The resulting cervically induced eye movements consisted of two components. In addition to a cervical nystagmus, with its slow, compensatory phase, a deviation of the mean eye position (shift) in an anticompensatory direction, opposite to trunk rotation was observed. The COR in relation to different neck torsion velocities distinctly showed a tuning curve with maximum reactions between 4 degrees/s and 9 degrees/s. Above these values, a strong decrease in COR resulted. The optimal working range vastly differs from that of the vestibulo-ocular reflex (VOR).

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Cervically induced eye movements can be observed when the trunk is rotated and the head fixed. In most test situations, rotating chair motion and head fixation are carried out manually. As a result, specific and non-specific sources of error are involved in these procedures that hamper the reproducibility of test conditions. A system is described that provides quantifiable and reproducible, electronically controlled movements of the rotating chair. Ramp and rectangular stimulus profiles are achieved by infrared optical gate devices on the chair axis. Various processor-controlled sequences of angular displacement and duration can be programmed and monitoring of chair movement is available to the operator during testing, which is otherwise performed in complete darkness. Individual casts of the upper jaw connected with a telescope wall clamp facilitate optimal head fixation. Since great caution is required when using an electronically controlled chair for such tests, and the possibility of damage to the vertebral column is increased by head fixation, several devices have been incorporated into the equipment to fulfil safety requirements such as release mechanism in the head fixation system, besides other safety devices. This system enables cervically induced eye movements which can be related to amplitude, acceleration and velocity of trunk rotation. The results are important for direction and extent of eye shifts, nystagmus and circular-vection.

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Using the 31-Phosphorus pulsed NMR-technique by FFT information processing it was possible to obtain the following results: The phosphorus compounds were measured as time function in the course of 24 h in isolated skeletal and cardiac muscle of rana temporaria in a dynamic NMR experiment. The shift of the observed resonance lines by increasing intracellular H+ concentration during anoxic conditions will be described in this paper in accordance with the NMR literature. The time course of the beta group of ATP (which is representative for ATP) has been found not to decrease monotonically but rather periodically in a half-hour periodicity until finally a complete fading of ATP in the NMR spectrogram occurs. Besides the resonances described in the literature it was possible to record two additional unknown resonance lines 1.6 and 4.6 ppm apart from the classical alpha- and beta ATP peaks. The peak area of this up to now unknown substance followed a periodic law, regarding the first 2-3 h after preparation. Afterward the concentration dropped to zero. Some shift of the resonance lines of the NMR spectrum could be observed dependent upon the fact that in the muscle cell the ATP normally occurs as a complex with Mg++ ions (MgATP). After separation of Mg++ ions from ATP at low intracellular pH values the resonance lines shifted by some 1-4 ppm. This was tested by test solutions containing MgATP as a complex of free ATP. Although this observation could not sufficiently explain the two as yet unknown lines in the NMR spectra, this result gave rise to further exploration of the phenomenon. To explain the unknown resonance lines, the spectra of the heart and skeletal muscle were compared with that of an adenosine tetraphosphate solution. Based upon the fact that the frequencies of the lines under discussion are identical with those of the adenosine tetraphosphate, one can conclude with a high degree of probability that the as yet unknown lines are originated by adenosine tetraphosphate. If this hypothesis is correct, the concentration of adenosine tetraphosphate could be determined in the order of 1 mM, thus being one third or one quarter of the concentration of the adenosine triphosphate. To give better evidence for the clarification of the newly found substance it will be necessary to record under identical experimental conditions 1H and 13C NMR spectra during the time course of deterioration of the skeletal and cardiac muscle.(ABSTRACT TRUNCATED AT 400 WORDS)

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Human retinal oscillatory potentials in response to an alternating checker-board pattern stimulus were studied in two subjects over an intensity range of 7.5 log units. Under scotopic conditions, two wavelets (S1 and S2) could be recorded. At an intensity of 1.9 photopic log Td four high frequency oscillations (O1--O4) were noticed and a discontinuity was observed in the corresponding luminance curve of the b-wave together with a sudden decrease in the magnitude of the standard deviation of the amplitude measures. The oscillations were noticed only on the ascending slope of the b-wave. With increasing stimulus intensity, their latency decreased at a slower rate than that of the b-wave and their number decreased. Each wavelet had an amplitude maximum at a certain stimulus intensity level. It was suggested that O1--O4 were generated by the activation of the photopic system and that S1 and S2 were of scotopic origin.

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