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Biomedical subjects

V Di Maio

Publications and source records attributed to V Di Maio.

At least 19 recordsLinked to original sources

Allogeneic gene-modified tumour cells in metastatic kidney cancer. Report II.

In a limited study, comprising only ten patients, we have previously reported that allogeneic irradiated RCC-cell-line cells, engineered to produce IL-2 (ACHN-IL-2), admixed with autologous metastatic formalin-treated tumour cells were used to vaccinate MRCC patients in progression of disease and also receiving IL-2 immunotherapy. The cells, admixed to autologous TC, were administered subcutaneously. We now report an extended study on thirty patients and one hundred thirty-one controls. Patients received 4-20 injections (mean 10 +/- 4), containing an average of 92 x 10(6) +/- 45 x 10(6) ACHN-IL-2 transfected cells (a minimum of 25 x 10(6), and a maximum of 200 x 10(6)). Autologous TC, admixed to allogeneic, were also administered by 4-16 s.c. injections (mean 7 +/- 3), i.e. a total of 12 x 10(6)-160 x 10(6) cells. Vaccination was administered during 73-1451 (307 +/- 316) days, and the follow-up continued for 1122 +/- 1240 days (106-5137). Throughout this period, the patients continued receiving the previously set immunotherapy treatment. No adverse side effects related to the treatment were noticed. One complete and four partial tumour responses were observed, as well as nine cases of stable disease. Thirteen patients died in the treated group (43%) and 63 (44%) in the control group. Responding patients resumed progression in 4-11 months and died 18 and 36 months after beginning the vaccine therapy. The Gehan Wilcoxon's test showed a significantly (P < 0.01) better survival in the vaccinated patients compared to that of the controls. Thus, we confirm, in an increased number of patients and an extensive follow-up, that our vaccination protocol is safe, devoid of adverse side effects, and promising.

Adult↗

Different types of noise in leaky integrate-and-fire model of neuronal dynamics with discrete periodical input.

Different variants of stochastic leaky integrate-and-fire model for the membrane depolarisation of neurons are investigated. The model is driven by a constant input and equidistant pulses of fixed amplitude. These two types of signal are considered under the influence of three types of noise: white noise, jitter on interpulse distance, and noise in the amplitude of pulses. The results of computational experiments demonstrate the enhancement of the signal by noise in subthreshold regime and deterioration of the signal if it is sufficiently strong to carry the information in absence of noise. Our study holds mainly to central neurons that process discrete pulses although an application in sensory system is also available.

Action Potentials↗

Allogeneic gene-modified tumour cells in metastatic kidney cancer. Preliminary report.

An allogeneic irradiated RCC cell line, engineered to produce IL-2 (ACHN-IL-2), admixed with autologous metastatic formalin-treated tumour cells, was used to vaccinate ten MRCC patients in progression of disease in spite of IL-2 immunotherapy. The cells were administered subcutaneously and/or intra-tumourally. Sixty-four MRCC patients in progressive disease, not treated by vaccination but receiving similar IL-2 immunotherapy, were considered as the control group. Patients received 4-16 injections (mean 9 +/- 4), containing an average of 10.6 x 10(7) +/- 7.7 x 10(7) ACHN-IL-2-transfected cells (a minimum of 4 x 10(7), and a maximum of 31 x 10(7)). Four patients also received intra-tumour injections. Vaccination was administered during 30-418 days, and the follow-up continued for 649 +/- 353 days (190-1342). Throughout this period, the patients continued receiving the previously set immunotherapy treatment. No adverse side effects related to the treatment were observed. One complete and one partial tumour response were observed, as well as two stable and one no-relapse disease. All but one patient died. Responding patients resumed progression in 4-11 months and died 18 and 36 months after beginning the vaccine therapy. In spite of the small number of treated patients, Wilcoxon's test showed a significant (P < 0.05) improvement of the survival in the vaccinated group compared to that of the control. The described vaccination protocol seems safe, devoid of adverse side effects and promising. It warrants further investigation.

Aged↗

A Brownian simulation model of glutamate synaptic diffusion in the femtosecond time scale.

To gain a better understanding of the elementary unit of synaptic communication between hippocampal neurons, we simulated the release of glutamate from a single pre-synaptic vesicle and its diffusion into the synaptic cleft. Diffusion of glutamate was simulated by a Brownian model based on Langevin equations. The model was implemented for parallel computer simulation and tested under different conditions of glutamate release and different geometrical and physical characteristics of the synaptic cleft. All the tested parameters have shown to be important for the synaptic responses. The results show that the synaptic transmission efficacy is influenced by many different geometrical parameters and, as a consequence, the quality of the excitatory postsynaptic response can be very different in the same synapse. The variability in the quantal response found by several authors can also be explained by physical parameters other than by variations in the quantal content of the synaptic vesicle as proposed by these authors.

Animals↗

Threshold effect in visual perception of geometrical figures.

Filtering of the input image has been shown to play a central role in several aspects of visual perception. In our experiments in visual perception of the area of geometrical figures the orientation in random dot patterns, and some visual illusions, we have shown that a threshold effect inferred from the filtering of the input image produces a perceptual error. This error has been explained by using the concept of Image Function. The present paper is a brief review of our experimental results and of the models we have proposed.

Humans↗

The Müller-Lyer illusion in interpolated figures.

The Müller-Lyer patterns formed by separate dots have been used as stimuli in an experiment on visual perception to assess the influence of the number of dots composing the figures on the magnitude of the illusion. As predicted by our model, based on the Image Function theory, an increase was noted in the magnitude of illusion when the number of dots composing the arrowheads was increased. It follows from the model that filtering of the input image plays a central role in the formation of the illusion.

Adult↗

Visual perception of area and hypnotic susceptibility.

The visual perception of area of geometrical figures was compared for subjects of high and low hypnotizability in experiments with direct comparison of two different geometrical figures. The Stanford Hypnotic Susceptibility Scale (Form C) was used to assess subjects' hypnotizability. No differences between 17 highly hypnotizable and 10 low hypnotizable subjects were found. Present results were also compared with those previously obtained for subjects of unknown hypnotizability. The model based on the Image Function Theory proposed earlier to explain the errors in area estimation committed by subjects of unknown hypnotizability was confirmed as a general rule.

Adult↗

A computer program to study the area perception of squares and rectangles.

A computerized approach to study the visual perception of rectangles and squares is proposed. A program has been used for comparison of these two figures when one of them is fixed in size while the other is varied actively by a subject to match the area of the fixed one. The final errors on area and on perimeter made by the subject are computed for each pair of presented figures. The program is menu driven and thus easy to use by the investigator. Since the task procedure is very simple and non-obtrusive to the subjects, it can be used both for children and adults as well as for normal and brain impaired subjects in order to study some perceptive and cognitive functions. This program recognizes the most common graphics cards used by computers running under MS-DOS to adjust the parameters of the presented figures according to the pixel resolution of the graphics card. Quick-BASIC was used to write the program which was compiled by Microsoft Professional Basic 7.0 compiler.

Adult↗

A model of the perception of area.

A psychophysical experiment was performed to measure the ability of human observers to compare the areas of two geometrical figures (squares and rectangles). The results show a systematic overestimation of rectangle area with respect to that of the squares. A formal model of area perception and its consequent estimation is proposed, which is based on the concept of an 'image function'. It assumes that not the original figure but some specific isocline defined on the image function surface determines area perception. The systematic error observed in the experiment is explained by the model. We discuss the role of different definitions of the image function as well as its parameters on the model performance.

Adult↗

Matching the orientation of dot patterns with real, interpolated, and extrapolated lines.

The perception of the orientation of random-dot patterns was studied using four different matching tasks. Homogeneous, elongated patterns and patterns containing Moiré effects were used. One of the tasks implied linear extrapolation and two others implied linear interpolation of the matching line. The fourth task was identical with those used in previous studies by the authors on this topic. Systematic deviations from the axes of orientation of the patterns were observed for the latter task when compared with the former ones. When a short matching line, implying linear extrapolation, was used performance by subjects tended to be more inaccurate than in the other matching tasks. The linear interpolation tasks, in which the matching line was determined by either two collinear distant short lines or by two distant dots, provided more accurate and stable performance than the other two tasks. The results are discussed from the point of view of global orientation perception derived from an image function of the stimuli.

Adult↗

Area perception in simple geometrical figures.

The results of experiments on visual perception of area of circles and squares are reported. Pairs of geometrical figures were presented simultaneously on an oscilloscope screen. While one of them was fixed, the other one was controlled by an experimental subject. The task of the subject was to match the area of the variable figure to the area of the fixed one. The obtained data show underestimation of the area of circle when compared with square. A mathematical model designed to explain this phenomenon is proposed here. The image function defined as a low-pass filtered (blurred) version of the figure is employed for this purpose. Then, instead of the position of the image function maxima, the position of a threshold value is used for area computation.

Adolescent↗

The direct effect of the thyroid hormone on cardiac chronotropism.

To establish whether thyroid hormone modifies the heart rate directly or through an action on other neuroendocrine modulators, the authors have examined several animals models differing in the plasma levels of such compounds. Induction of the hypothyroid state in rats produced a slow onset of bradycardia, which may be removed by a prolonged triiodothyronine treatment. The involvement of TSH was excluded as, by comparing thyroidectomized, hypophysectomized and cold exposed rats, the heart rate was found to vary according to the thyroid levels and not to the TSH levels. Moreover growth hormone, corticotropin and gonadotropins do not influence the heart rate, as the bradycardia induced by hypophysectomy was fully removed by triiodothyronine treatment. The lack of influence by ACTH and GnH was confirmed by treatment of thyroidectomized rats with corticosteroids or testosterone, respectively. Finally, thyroid hormone did not act on the heart rate by changing the norepinephrine output at the sympathetic nerve endings in the heart. In fact, thyroidectomy produced a more intense bradycardia than sympathectomy, and such bradycardia was equally removed by triiodothyronine treatment in thyroidectomized rats and in thyroidectomized and then sympathectomized ones. The authors suggest that the direct effect of the thyroid hormone on cardiac chronotropism is due to an early enhancement of beta-adrenoceptors, followed by a late modification of the electrophysiological properties of the myocardium.

Animals↗

Thyroid hormone and the mitochondrial population in the rat heart.

The effects of the thyroid hormone on the number and protein content of mitochondria were investigated in rat heart. The specific mitochondrial population, determined by direct counting, was estimated to be about 3.7 X 10(11) mitochondria per g wet weight in young hypothyroid male rats (T) and about 2.4 X 10(11) (65%) in euthyroid animals, sex- and age-matched. Triiodothyronine (T3) treatment of T animals restored the levels to normal values. The protein content per mitochondrion, on the contrary, was higher in euthyroid animals or hypothyroid animals, following T3 treatment, compared to T. Finally, thyroid hormone enhanced the heart mass and, therefore, the cardiocytal and mitochondrial populations of the whole organ. These results differ from previous data from our laboratory indicating that liver weight is increased by thyroid treatment, albeit at a slower rate, while the number of mitochondria per g tissue increases and the protein content per mitochondrion decreases. In conclusion, the effects of the thyroid hormone on mitochondria are different in the hepatocyte and in the cardiocyte. It appears that the hormone differently modulates the machinery of mitochondrial protein synthesis in the two target cells according to the physiological role of mitochondria in liver and heart cells, i.e. heat production or mechanical energy output, respectively.

Animals↗

Further evidence of benzene carcinogenicity. Results on Wistar rats and Swiss mice treated by ingestion.

Wistar rats and Swiss mice were treated by ingestion (stomach tube) with benzene in olive oil at a dose of 500 and 0 mg/kg b.w. once daily, 4-5 days weekly, for 104 weeks (rats) or for 78 weeks (mice). In Wistar rats, benzene caused Zymbal gland carcinomas, carcinomas of the oral cavity, and carcinomas of the nasal cavities, and an increase in the incidence of total malignant tumors. In Swiss mice, benzene produced Zymbal gland carcinomas and dysplasias and an increase in the incidence of mammary carcinomas (in females), lung tumors, and total malignant tumors. These experiments further confirm that benzene is a multipotential carcinogen as was shown before by long-term bioassays performed on Sprague-Dawley rats in the same Experimental Unit.

Administration, Oral↗

Civilian gunshot wounds of the brain.

The authors report on 42 fatal gunshot wounds to the brain in civilians. The firearms used were those commonly available to civilians, ranging from a .22 revolver to a .45 semiautomatic pistol. Missle tracks were measured and the volume computed. The relatively low-velocity missles produced by these weapons to not create the devastation that characterizes wounds from high-velocity military firearms. Instead, there is much variation in the size of the missle tracks, and they cannot be directly related to caliber. Pressure marks and contusions, impaction of bone chips, internal richochet, and cerebral edema occurred frequently. The missle passed through the brain completely in very case but was retained by the skull or soft tissues in a large percentage of cases. The mechanism of death may be acute pressure on the brain stem from the passage of the missle through the brain.

Adolescent↗

Modulation of membrane potential in algal cells by temperature gradients. A thermodynamic approach.

The aim of the present study is to ascertain whether transmembrane temperature gradients couple with transport of electric charge in living cells of Valonia utricularis and eventually measure the thermodynamic coupling coefficient (s). Simple experimental procedures are described that allow generation of temperature gradients of predetermined sense and intensity across the cell membrane. Simultaneous measurement of the potential difference is ensured by standard electrophysiological methods. The mathematical expressions that allow quantitative treatment of experimental results are indicated in the article and are based on standard nonequilibrium thermodynamic and electrophysiological formalism. The value of the coupling coefficient between temperature gradient and flow of electric charge is indicated and concisely discussed in terms of possible mechanisms of ionic membrane transport.

Biological Transport↗

A Brownian model of glutamate diffusion in excitatory synapses of hippocampus.

We simulated the diffusion of glutamate, following the release of a single vesicle from a pre-synaptic terminal, in the synaptic cleft by using a Brownian diffusion model based on Langevin equations. The synaptic concentration time course and the time course of quantal excitatory post-synaptic current have been analyzed. The results showed that they depend on the number of receptors located at post-synaptic membrane. Their time course are dependent both on the total number of the post-synaptic receptors and on the eccentricity of the pre-synaptic glutamate vesicle.

Glutamic Acid↗