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Biomedical subjects

A Bertuzzi

Publications and source records attributed to A Bertuzzi.

At least 37 records · Page 2Linked to original sources

Kinetic and survival response of the M14 cell line to lonidamine associated with adriamycin or hyperthermia.

Lonidamine (LND), an indazole-carboxylic acid derivative, was delivered alone and together with adriamycin (ADM) or hyperthermia to the human melanoma cell line M14, and cell survival was assessed. Cell cycle-specific effects were investigated by analyzing sequences of DNA content histograms by means of a suitable mathematical procedure. LND delivered for 1 h at a dose of 50 micrograms/ml did not affect proliferation and survival of the cells. Exposure of the cells for 1 h to ADM (1.0 microgram/ml) followed by LND for 1 h (50 micrograms/ml) produced the highest effect on the survival. Kinetic parameters were affected by the combined treatment slightly more than by ADM exposure alone. Simultaneous delivery of LND (50 micrograms/ml) with hyperthermia (42 degrees C, 1 h) reduced the survival and enhanced the block of cells in the G2M phase, as compared with the heat treatment alone. The effect of the treatments on cell survival appeared to be related to the perturbation of the G2M phase of the cycle.

Antineoplastic Agents

Prediction of lithogenic character of human bile by a quaternary system.

The lithogenic character of human gallbladder bile was investigated by a mathematical model on the basis of a clinical data set. Each bile was described by means of the quaternary system bile salts--phospholipids--free fatty acids--cholesterol. Reporting a set of bile samples on the tetrahedron of concentrations, a clear separation emerged between the control bile, the bile from patients with gallstones, and the bile of subjects with gallbladder dyskinesia. This group was characterized by a largely increased content of free fatty acids.

Adult

Analysis of DNA synthesis rate of cultured cells from flow cytometric data.

The rate of DNA synthesis along S phase is estimated from flow cytometric histograms on the basis of a mathematical model of a cell population. In the absence of loss, the model expresses the population kinetics in terms of DNA synthesis rate, S-phase influx, and population size. A single histogram is sufficient to determine the DNA synthesis rate when the population is in balanced exponential growth. Two suitably chosen histograms are necessary if the S-phase influx is exponential in a time interval longer than the S-phase duration. The analysis procedure was tested on published autoradiographic data and applied to three cultured cell lines (CM-S, 3LL, and M14 cells) that show various patterns of DNA distribution. In each case the cell-cycle fractions, the DNA synthesis rate, and the S-phase duration were obtained.

Animals

A general expression for sequential DNA-fluorescence histograms.

A general expression for time sequences of DNA-fluorescence histograms from flow microfluorometry is given in this paper. Such expression is given in terms of the law of DNA growth along S phase, the flux of cells into S, and the efflux out of M. Special conditions of growth (e.g. the exponential steady-state growth), and the case of blocks in S phase are also analyzed. Some simulations of the expressions obtained are presented.

Cells, Cultured

Estimation of cell DNA synthesis rate from flow-cytometric histograms.

The rate of DNA synthesis along S-phase can be estimated on the basis of a simple model of a cell population, from a single FCM histogram under conditions of balanced exponential growth, and from two histograms suitably spaced in time under conditions of locally exponential S-phase influx. An algorithm that constructs a piecewise constant approximation of the synthesis rate and estimates the phase fractions from a single histogram is presented. The results of the application of the algorithm to a set of computer generated histograms in balanced exponential growth are reported.

Animals

Peristaltic transport of a solid bolus.

An analysis of the peristaltic propulsion of a solid spherical bolus enclosed in a contractile membrane is presented. The model is based on in vitro preparations of intestinal segments, and utilizes a simplified representation of the mechanical properties of the muscular coats of the wall. The sequence of deformed configurations of the membrane and the displacement of the bolus are obtained by numerical solution of the model equations. The analysis presented in this paper could be useful for other studies in biomechanics (e.g. uterine contraction and motion of red blood cells in narrow capillaries).

Gastrointestinal Motility

Some parameters of descending inhibition during colonic propulsion.

Isolated segments of rabbit distal colon were stimulated by distension of intraluminal balloons, with the aim of investigating the electrophysiological pattern of descending inhibition (DI) during the peristaltic reflex. Incidence, duration, and latency of DI were studied by varying the parameters of stimulation. A linear correlation was found between stimulus duration and DI duration for stimuli up to 10 s long. DI duration increased with the distance of the recording site from the stimulus up to 3 cm. A more complex relation was found between balloon volume and DI duration. Propagation velocity decreased with the distance from the stimulus. The relation between ascending excitation and DI was also studied: ascending excitation could always be suppressed by DI. DI was examined after addition of anticholinergics, ganglionic blocking agents, and tetrodotoxin to the organ bath. The results show that DI parameters are partially related to the stimulus characteristics and that propagation of DI is neurally mediated through nonadrenergic inhibitory nerves.

Animals

Evaluation of doxorubicin cardiotoxicity in patients treated intermittently with beta-methyldigoxin.

Twenty-one patients with various advanced neoplasms were treated with 60 to 75 mg/m2 of doxorubicin every 3 to 4 weeks and monitored by ECG and systolic time intervals (PEP/LVET) with the aim to establish whether a pretreatment with beta-methyldigoxin, administered intermittently, could prevent doxorubicin-induced cardiotoxicity. It was found that until patients received digitalis pretreatment the PEP/LVET ratio did not change significantly from mean basal values even after the highest cumulative dosages of doxorubicin. However, after interruption of the therapy with both drugs, PEP/LVET increased reaching a value not significantly different from that observed in a comparable group of patients treated only with doxorubicin. Moreover, of 9 patients who reached the cumulative limiting dose, 2 developed congestive heart failure. These results question the possibility that digitalis administered according to an intermittent treatment scheme may prevent doxorubicin cardiomyopathy.

Adolescent

Relationship among estrogen receptors, proliferative activity and menopausal status in breast cancer.

Kinetic and estrogen receptor (ER) determinations were performed on 357 primary breast cancers. The proliferative activity of the cell population was determined by the autoradiographic technique and expressed as [3H]thymidine labeling index (LI): the ER status was assessed by the absorption charcoal technique. From the overall analysis of the relationship between proliferative activity and ER status, by using the median LI value as cutoff of low and high proliferating tumors, a correlation between ER + status and low proliferative activity and between ER- status and high proliferative activity was observed in 64% of the cases. Menopausal status proved to be an important determinant of kinetic and ER features. In fact, the proliferative activity was always higher in ER--tumors than in ER + tumors within the same menopausal group, and a decrease in proliferative activity was observed from premenopause to postmenopause within ER + and ER--tumors. The analysis of the relation between ER levels and proliferative activity in ER + tumors also evidenced three main ER/LI clusters significantly related to premenopause, paramenopause and postmenopause. A particular indication of nodal involvement was evidenced for a cluster of tumors with low ER levels and high LI from postmenopausal patients. The three different, previously proposed kinetic groups of potential relevance for prognostic and therapeutic purposes were confirmed and more precisely defined by considering not only premenopause and postmenopause but also paramenopause.

Adult

Estrogen receptors in renal carcinoma.

The presence of estrogen receptors was determined in 31 cases of renal carcinoma by use of the charcoal absorption technique. In 26 of these cases, the 'normal' counterpart of the same kidney was also studied. In 13 normal and in 19 neoplastic samples, the values were undetectable; in the other cases, the values were very low. Progesterone and dihydrotestosterone receptors were also studied in four cses (both normal and neoplastic tissue) by use of a gel-filtration assay: all the samples were negative. These findings do not support the presence of significant amounts of estrogen receptors in kidney carcinoma.

Charcoal

Clinical data and estradiol receptor evaluation in breast cancer biopsies.

To determine the correlation between the response to the estradiol receptor test and some fundamental properties of the tumor and the host, a study was conducted on 337 patients. Primary carcinomas, including lobular carcinomas, and recurrences or metastases are characterized by similar frequencies of response to the estradiol receptor test (68% positive, 26% negative and 6% borderline), while normal breast tissue is characterized by a higher frequency of negative results (3% positive, 71% negative and 26% borderline). Postmenopausal patients show a shift of estradiol receptor levels towards higher values with respect to premenopausal patients. Contemporaneously, an increase in estradiol receptor concentrations with patient age is observed. The clinical stage appears in influence estradiol receptor content only in postmenopausal patients, for whom an increase in the tumor size is accompanied by a decrease in the estradiol receptor levels. The apparent association constant of the receptors assumes values ranging from 1.5 to about 300 X 10(9) M-1 and does not appear to be related to either the type of tumor tissue or to the clinical stage of the tumor, age, or menopausal status of the patients.

Adult

Evaluation of cardiac activity and pharmacokinetic analysis of 3H-adriamycin in patients pretreated with beta-methyldigoxin.

The consequences at the cardiac level of adriamycin treatment alone or in association with the cardiac glycoside beta-methyldigoxin, were evaluated with reference to the PEP/LVET ratio, heart rate, and minimum blood pressure. The variation usually seen in the PEP/LVET ratio when adriamycin is administered alone was not observed when pretreatment with beta-methyldigoxin was also given. A similar situation is found with variations in blood pressure and heart rate. From a pharmacokinetic point of view, this treatment scheme does not seem to affect the general behavior of the antibiotic.

Adult

An analysis of the peristaltic reflex.

A mathematical model describing the dynamics of the peristaltic reflex in an isolated intestinal segment is presented. The model is referred to a preparation that makes it possible to record the relevant mechanical and electrical variables during the course of the reflex. A simplified representation is used for the structure and the operation of the intrinsic nervous plexus, but the interaction between mechanical and elctrical events appears quite clearly and some features of the experimental data are well predicted.

Biomechanical Phenomena

Peristalsis in distal colon of the rabbit: an analysis of mechanical events.

The mechanical behavior of isolated segments of rabbit distal colon was studied by experimental and theoretical techniques. The isometric isovolumic preparation was adopted to obtain records of endoluminal pressure, force, and wall morphology during 59 spontaneous and 53 electrostimulated peristaltic contractions. On strips of longitudinal and circular muscle, excised from the same segments, the tension-velocity and tension-length relationships were also measured. To describe mechanical events occurring during propulsion, a mathematical model was developed that incorporates the measured characteristics of the muscle. In response to given waveforms for the activation of the two muscular coats, the solution of model equations provides the time courses of pressure, force, and wall morphology. A number of parameters measured in the experimental contractions (e.g., pressure and force peaks, time lag between the stimulus and the peaks, velocity of progression of the peristaltic wave) were compared with model outputs, and a similar pattern of response was found. Therefore the model made it possible to relate segment and strip experimental data and to investigate the temporal and quantitative relationship between the contraction of longitudinal and circular layer.

Animals

An improved criterion for the evaluation of estrogen receptor binding data in human breast cancer.

The evaluation of the data is an important step in performing the estrogen receptor test. For this reason an effort has been made to derive a more reliable threshold criteria. Among the parameters considered, Xo, Ka, and BI%, only the former 2 appear to be suitable to allow a proper evaluation of the results. From the analysis of different types of carcinomatous or normal breast specimens, limit values of these parameters have been recovered for positivity and negativity of the estrogen receptor test. We found all the samples showing Ka less than 1.5 x 10(9) M-1 or Xo less than 5 fmol/mg proteins to be negative, those characterized by low values of both the parameters were borderline, and all the remaining ones were positive.

Breast Neoplasms