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Biomedical subjects

L Barrios

Publications and source records attributed to L Barrios.

At least 55 records · Page 3Linked to original sources

Chromosomal instability in breast cancer patients.

We have carried out cytogenetic studies, using the G-banding technique, in peripheral blood lymphocytes of 10 patients affected by breast carcinoma. The frequency of aberrant metaphases (7.36%) is significantly different from that of our laboratory controls (3.76% of aberrant metaphases) but not from that detected in patients suffering from bladder cancer (10.64%) and Hodgkin's disease (11.03%), two conditions that have previously been described as chromosomally unstable. Our results suggest that breast carcinoma patients show a degree of chromosomal instability that could be related to a predisposition to neoplastic disease.

Adult↗

Chromosome instability in bladder carcinoma patients.

The relationship between the presence of a high frequency of chromosome aberrations and a predisposition to cancer has been well established in the so-called chromosome instability syndromes. Chromosome instability is also present in a variety of patients affected by cancer, and sometimes in their healthy relatives. We present a cytogenetic study carried out in lymphocytes from 13 untreated bladder carcinoma patients (only four of them had a history of occupational exposure to mutagens). Percentages of aberrant metaphases were significantly higher in cancer patients than in controls. Of the total number of chromosome aberrations in cancer patients, 67.16% corresponded to major structural chromosome abnormalities, while 25.37% were gaps or breaks. Numerical abnormalities represented 7.46% of the total. The bands more frequently involved in chromosome rearrangements were 5q31 and 1q32. Our results tentatively indicate that a significant proportion of patients with bladder carcinoma may have an underlying inherent chromosome instability. An age effect cannot be excluded, but we did not find significant differences between patients over 50 years of age and patients under 50 years of age.

Adult↗

Telomere association of chromosomes induced by aphidicolin in a normal individual.

Telomere association of chromosomes of a phenotypically and mentally normal individual was detected in 11.7% of metaphases cultured in RPMI-1640 with aphidicolin. No preferential involvement of any chromosome pair was detected. In two other individuals the frequency of telomere associations was much lower (1.9% and 0.7% respectively) under the same culture conditions. In the first individual the high number of telomere associations in cultures with aphidicolin along with the presence of telomere association (2.4%) in cultures with F.10 medium alone could reflect a constitutional telomere anomaly that is more often expressed in the presence of aphidicolin.

Aphidicolin↗

Lymphocyte and sperm chromosome studies in cancer-treated men.

To evaluate the reliability of the quantitative extrapolation of the long-term effect of cancer therapies from somatic cells to germ cells, we compared the frequency of chromosome abnormalities in 303 lymphocytes from four individuals treated with radio- and/or chemotherapy 5-18 years earlier with the frequency in 422 spermatozoa from the same individuals. The mean frequency of structurally abnormal complements was much higher in germ cells than in somatic cells (P = 2.08 x 10(-6)). The fact that spermatogenic cells share cytoplasm is suggested as a possible factor in the increased viability of germ cells with chromosome aberrations. In addition, in spermatozoa the incidence of structural chromosome abnormalities was much higher in treated individuals than in controls (P less than 0.00060), while in lymphocytes no statistically significant differences could be observed. This observation and the apparent lack of relationship between individual frequencies in the two kinds of cells suggest that the long-term effect of anti-tumor treatments on germ cells cannot be extrapolated from the analysis of somatic cells.

Antineoplastic Combined Chemotherapy Protocols↗

Cytogenetic effects of radiotherapy: frequency and types of chromosome aberrations.

The frequency and types of chromosome aberrations induced by ionizing radiation in cancer patients were evaluated in 24 cases studied just before and immediately after radiotherapy. The incidence of aberrant metaphases prior to treatment was 9.98% and increased significantly after treatment to 32.8%. The frequency of chromosome aberrations before radiotherapy was, with the exception of the cases of breast cancer and seminoma, significantly higher than that in our laboratory controls. A comparison of chromosome abnormalities observed before and after treatment indicated that dicentric translocations, rings, and reciprocal translocations increased by a factor of 23, 13, and 11, respectively, after radiotherapy. Ionizing radiation produces more asymmetrical than symmetrical chromosome aberrations and more two-break than one-break anomalies.

Adult↗

Fragile sites and breakpoints in constitutional rearrangements and in human sperm chromosomes.

Recently, it has been suggested that an association exists between breakpoints involved in constitutional rearrangements and fragile sites; however, statistical analyses of this relationship are controversial. We have analyzed 1200 breakpoint from different constitutional rearrangements, 1522 breakpoints with respect to their recurrence and 217 breakpoints from sperm chromosomes as reported by several authors. The coincidence between breakpoints and fragile sites was 35.3%, 43.6% and 41.9% respectively. The statistical significance of these coincidences depends on whether factors such as the relative length of the bands or the recurrence of the rearrangements are taken into account.

Chromosome Aberrations↗

Expression of folate-sensitive fragile sites in lymphocyte chromosomes.

The expression of folate-sensitive fragile sites (FS) was analyzed using MTX as a fragility inducer in seven normal subjects [four unrelated persons and three members of one family (father, mother, and son)]; a woman heterozygous for fra Xq27.3 with a 47,XXX karyotype; and her son, affected by the fra-X syndrome. The mean expression of chromosome lesions (CL) other than Xq27.3 was 70.1% (686CL in 978 metaphases), and the coincidence between CL and FS was 68.9%. We propose six new c-fra sites: bands 4q33 and 11q22 because they were found in two members of the same family; band 13q32 because it had a frequency of expression of 3% of metaphases; and bands 3p13, 8q21, and Xq21 because they were observed in four of the nine individuals studied.

Adult↗

Cytogenetic effects of radiotherapy. Breakpoint distribution in induced chromosome aberrations.

A total of 660 breakpoints were identified in the chromosome aberrations detected in lymphocytes from cancer patients after radiotherapy. The results show that chromosomes 1, 3, and 7 were significantly more affected than other chromosomes by ionizing radiation in vivo. Chromosome arms 1p, 1q, 7q, and 11p were also significantly more affected. Some bands also showed a special sensitivity to radiation, and band 1q32 was the most affected. This band is proposed as a "hot point" for the clastogenic effect of ionizing radiation. A significant clustering of breakpoints in G bands was also found, especially at the telomeres, as previously described by other authors. Clustering of breakpoints was also observed in bands where fragile sites, protooncogenes, breakpoints involved in chromosomal cancer rearrangements, and breakpoints involved in chromosomal evolution of the Hominoidea are located.

Adult↗

Activity of the gamma-glutamyltransferase, leucine aminopeptidase and alkaline phosphatase enzymes in human tear fluid.

In this work the presence of gamma-glutamyltransferase (GGT), leucine amino-peptidase (LAP) and alkaline phosphatase (AP) is shown in human tear fluid. We studied these levels according to sex, age and some eye refraction defects. The differences between the levels for both sexes are not significant. LAP and AP do not show any differences in either age groups or individuals with some refraction defects. The average level of GGT is higher from 40 years of age upwards (p less than 0.005). In individuals with refraction defects, the enzymatic activity is significantly higher (p less than 0.05) than the activities found in normal subjects. The levels of the three enzymes in serum and tear fluid do not show a significant correlation nor are they significantly modified after the samples have been frozen for a month at -20 degrees C.

Adult↗

Can sister chromatid intercrossings be considered as prelesions?

In a study of the expression of folate-sensitive fragile sites in five normal individuals using RPMI medium containing methotrexate (MTX), we observed a high frequency of "sister chromatid intercrossings" (SCI) that is, the intersection of sister chromatids. The location of SCIs corresponded to fragile sites in 54.2% of the cases. Of the SCIs observed in each individual, 43%-53% were located at the same bands as their expressed fragile sites. Furthermore when RPMI + MTX medium was used instead of F-10 medium, the incidence of SCIs increased tenfold. We suggest that SCIs could indicate the existence of a pre-lesion.

Cells, Cultured↗

Chromosome abnormalities in peripheral blood lymphocytes from untreated Hodgkin's patients. A possible evidence for chromosome instability.

We describe the presence of a high frequency of spontaneous chromosome aberrations in lymphocytes from six untreated patients with Hodgkin's disease. The characteristics of the chromosome abnormalities observed suggest the existence of a certain degree of chromosome instability in these cases, that could be a predisposing factor for the development of malignancies.

Adolescent↗

A quantitative method for evaluating the effects of drugs on bone marrow cellularity using the same experimental animal. Quantification of the effects of a single dose of busulphan.

A method for quantifying the cellularity of rats bone marrow per unit of weight is described. Absolute numbers of each cell type per mg of bone marrow in the left and right femurs of the same experimental animal were determined at different times. In normal rats in which both femurs were studied simultaneously it was found that the absolute counts of each cell type per mg of bone marrow in the left and right femurs did not differ, nor were differences found in absolute numbers of marrow cells when the quantitative analyses from the left femurs were compared with those of the right femurs of the same animal, 10 and 20 days later. In order to test the validity of the present method for evaluating the effects of drugs on hematopoiesis, a single oral dose of busulphan (20 mg/kg), was administered to normal rats immediately after the marrow quantitative studies of the left femurs were performed. A marked and significant reduction in total nucleated cell was seen in marrows from the right femurs, 10 days later. Cellular effects were particularly pronounced on the myeloid line. Results presented here indicate that the quantitative study employed is a simple and useful method to evaluate the effects of drugs on hematopoiesis. The novelty of this method lies in: 1) its expression of cellularity on a per mg marrow basis, thereby avoiding possible misinterpretations of data which occur when results are expressed as percentages and 2) the analysis of contralateral femoral marrow specimens obtained from the same animal before and after drugs treatment. Therefore, each animal acts as its own control avoiding possible errors in the determination of drug-induced hematopoietic changes due to inter-animal variability.

Animals↗

Erythropoietic action of dexamethasone on the anemia associated with an experimental chronic renal failure.

Partially nephrectomized anemic uremic rats were injected with dexamethasone phosphate (10, 50 and 500 micrograms/kg/day), i.p., and erythropoietin (5 U/day), s.c., for 10 days. A marked and usually significant stimulatory effect on erythropoiesis was seen in all uremic animals treated. Administration of erythropoietin and dexamethasone produced a pronounced increment in hemoglobin, hematocrit and circulating reticulocytes. The increase in red blood cell production was also evident through the generally increased absolute numbers of nucleated erythroid cell precursors per milligram of bone marrow. The highest increases were seen in the erythropoietin treated uremic rats. A dose effect correlation was apparent in uremic rats receiving 3 different doses of dexamethasone. Dexamethasone may stimulate erythropoiesis in our anemic uremic rats through a previous augmentation of erythropoietin production in the residual renal mass. A synergistic permissive effect of dexamethasone increasing the sensitivity of the erythropoietin-responsive cells to erythropoietin in bone marrow is also quite possible.

Anemia↗

Effects of xamoterol a new beta-adrenoceptor partial agonist, in patients with angina pectoris.

The effects of xamoterol on exercise capacity have been evaluated in 10 patients with angina pectoris and well-preserved left ventricular function. Compared to placebo a single 200 mg dose of xamoterol produced a slight but insignificant increase in exercise capacity. At maximum work load, ST-T segment depression was reduced (3 mm and 2.19 mm after placebo and xamoterol, respectively; p less than 0.05). The changes paralleled an insignificant reduction in maximal heart rate and pressure-rate product. At rest, xamoterol increased the heart rate from 80 to 86 beats/min. Thus, at rest, when sympathetic tone is low, xamoterol acts as a beta-receptor agonist but during exercise, when sympathetic tone is high, xamoterol acts as an antagonist and reduces myocardial ischaemia.

Adrenergic beta-Agonists↗

The mechanism of disappearance of the physiologic third heart sound with age.

To study the mechanism of disappearance of the physiologic third heart sound (S3) with advancing age, combined phonoechocardiographic and phonomechanocardiographic recordings from 165 normal subjects between 6 and 62 years old were quantitatively analyzed. Nearly all individuals under 40 years old had a recordable S3. Although recordable in 38.6% of the 44 subjects over 40 years old, the physiologic S3 found in adults was less intense and occurred later in diastole when compared with that in children and adolescents. Marked changes in left ventricular filling hemodynamics were observed with aging, including an increase in left ventricular wall thickness and mass, a prolongation of the left ventricular isovolumetric relaxation period, a decrease in left ventricular early diastolic filling and wall thinning rates, and a reduction in the height and steepness of the rapid filling wave measured on the calibrated left apexcardiogram (linear correlation with age significant at p less than .001 for all parameters). Although less pronounced, these changes were very similar to the diastolic abnormalities found in patients with pressure overload left ventricular hypertrophy. Therefore, the higher pressure load imposed on the left ventricular wall due to the well-known gradual increase in blood pressure that occurs during normal growth and adulthood appears to be the most likely explanation for the observed changes in diastolic filling. It is concluded that the later occurrence, the diminishing amplitude, and the eventual complete disappearance of the physiologic S3 with age results from a decrease in early diastolic left ventricular filling and subsequent deceleration of inflow caused by the development of relative left ventricular hypertrophy in adulthood as compared with childhood.

Adolescent↗