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Biomedical subjects

A Caballero

Publications and source records attributed to A Caballero.

At least 19 recordsLinked to original sources

The time of detection of recessive visible genes with non-random mating.

Expressions for the probability and average time of detection of a recessive visible gene in populations where there is partial selfing or partial full-sib mating are presented. A small increase in the proportion of inbred matings greatly reduces the average time until detection and increases the proportion detected. Unless the proportion of inbred matings or the population size is very small, the time and proportion detected are approximately independent of the population size.

Crosses, Genetic

Effective size of nonrandom mating populations.

Nonrandom mating whereby parents are related is expected to cause a reduction in effective population size because their gene frequencies are correlated and this will increase the genetic drift. The published equation for the variance effective size, Ne, which includes the possibility of nonrandom mating, does not take into account such a correlation, however. Further, previous equations to predict effective sizes in populations with partial sib mating are shown to be different, but also incorrect. In this paper, a corrected form of these equations is derived and checked by stochastic simulation. For the case of stable census number, N, and equal progeny distributions for each sex, the equation is [formula: see text], where Sk2 is the variance of family size and alpha is the departure from Hardy-Weinberg proportions. For a Poisson distribution of family size (Sk2 = 2), it reduces to Ne = N/(1 + alpha), as when inbreeding is due to selfing. When nonrandom mating occurs because there is a specified system of partial inbreeding every generation, alpha can be substituted by Wright's FIS statistic, to give the effective size as a function of the proportion of inbred mates.

Breeding

Effects of partial inbreeding on fixation rates and variation of mutant genes.

Diffusion methods were used to investigate the fixation probability, average time until fixation and extinction, and cumulative heterozygosity and genetic variance for single mutant genes in finite populations with partial inbreeding. The critical parameters in the approximation are the coefficient of inbreeding due to nonrandom mating (F) and the effective population size (Ne), which also depends on F and the variance of family size. For large Ns, the fixation probability (u) is u = 2(Ne/N)s (F + h - Fh), where N is the population census, s is the coefficient of selection of the mutant homozygote and h is the coefficient of dominance. For Poisson family size (independent Poisson distributions of selfed and nonselfed offspring with partial selfing, and independent Poisson distributions of male and female numbers with partial sib mating), Ne = N/(1 + F), and the time until fixation is approximately equal to Ne/N times the time to fixation with random mating, but this relation does not hold, however, for other distributions of family size. The cumulative nonadditive variance until fixation or loss for dominant genes is reduced with increasing F while for recessive genes it is increased with intermediate values of F. The average time until extinction of deleterious mutations is reduced by increasing F. This reduction, when expressed as a proportion, is approximately independent of the initial gene frequency as well as the selective disadvantage if this is large.

Animals

Decentration of intraocular lenses implanted after intercapsular cataract extraction (envelope technique).

Pseudophakos decentration produces symptoms such as glare, halos, and other visual aberrations. We have reviewed 161 eyes of patients who had an intercapsular cataract extraction with intraocular lens (IOL) implantation with a follow-up of at least six months. Mean decentration was 0.54 mm. It was 0.46 mm for the lenses implanted symmetrically in the bag, 0.65 mm for those implanted in the sulcus, and 0.91 mm for those implanted asymmetrically (bag-sulcus). The differences between the lenses fixated in the bag and those asymmetrically situated were statistically significant (P less than .001). Circular looped lenses (360-degree encircling loop) decentered less (mean 0.28 mm) than modified C-loop lenses (mean decentration 0.63 mm) and modified J-loop lenses (mean decentration 0.60 mm). These differences were statistically significant (P less than .001). The differences were also significant if we considered only the lenses implanted in the bag (mean decentration 0.20 versus 0.59 and 0.54, respectively) (P less than .0001).

Aged

The response to artificial selection from new mutations in Drosophila melanogaster.

Twenty generations of divergent selection for abdominal bristle number were carried out starting from a completely homozygous population of Drosophila melanogaster. All lines were selected with the same proportion (20%) but at two different numbers of selected parents of each sex (5 or 25). A significant response to selection was detected in eight lines (out of 40) and, in most cases, it could be wholly attributed to a single mutation of relatively large effect (0.5-2 phenotypic standard deviations). The ratio of new mutational variance to environmental variance was estimated to be (0.33 +/- 0.11) X 10(-3). The distribution of mutant effects was asymmetrical, both with respect to bristle number (85% of it was negative) and to fitness (most detected bristle mutations were lethal or semilethal). Moreover, this distribution was leptokurtic, due to the presence of major genes. Gene action on bristles ranged from additive to completely recessive, no epistatic interactions being found. In agreement with theory, larger responses in each direction were achieved by those lines selected at greater effective population sizes. Furthermore, the observed divergence between lines selected in opposite directions was proportional to their effective size, as predicted for mutations of large effect.

Animals

Effects of physical training during the growth on the granulation of myo-epithelioid cells of the rat kidney.

The behaviour of the granulation of the myo-epithelioid cells of the juxtaglomerular apparatus of the kidney and its relationship with the plasma concentrations of renin, sodium and potassium, and plasma osmolality have been studied in male and female Wistar rats that have been subjected to a programme of moderate physical exercise throughout their period of growth. In the trained rats a significant increase in the juxtaglomerular granulation index and a significant decrease in plasma renin concentration has been observed, the changes being more prominent in the female animals. Moreover in the trained rats significant increases in plasma sodium, potassium and osmolality have been observed.

Aging

[Hepatic activity of glutathione transferase and bromsulphalein metabolism].

The gluthatione transferase activity has been studied in liver biopsies from patients suffering with different hepatic lesion and related to the bromsulphalein (BSP) maximal transport (MT) and the conjugated dye present in serum. Results prove that the MT of BSP is independent of the enzyme activity, but is correlated to the conjugated BSP present in serum during the first perfusion. The enzyme activity, the MT of BSP and BSP conjugated rare in serum are not related to the liver lesion stage. From the analysis of our results we conclude that in the beginning the BSP conjugated proportion is determined by the enzyme activity which is not a restrictive factor of the BSP maximal transport.

Female

A weakly tumorigenic phenotype with high MHC class-I expression is associated with high metastatic potential after surgical removal of the primary murine fibrosarcoma.

We have examined the metastatic capacity of different clones of a chemically induced fibrosarcoma GR9. These clones have previously been characterized for their H-2 class-I and class-II phenotype, NK sensitivity and local tumor growth. Our present data show that clones which express low amounts of H-2 class-I antigens are poorly metastatic in a post-surgical spontaneous metastasis assay, while those expressing high levels of class-I antigens possess a high metastatic capacity. These results correlate inversely with local growth patterns of the clones. High metastatic capacity was associated with resistance to NK cells. In an experimental metastasis assay, based on intravenous administration of in vitro carried GR9 clones to syngeneic BALB/c mice, an opposite result to the post-surgical assay was obtained. Gamma-IFN treatment of B9 clones (H-2-deficient) enhanced H-2 class-I expression and diminished experimentally induced metastases. Metastatic colonies, from the spontaneous metastasis assay, obtained from different organs, showed changes in the ratio H-2K/H-2D. There was a tendency for down-regulation of the expression of H-2K molecules in H-2-positive clones and for up-regulation of H-2D expression in H-2-negative clones.

Animals

Chronic morphine administration in cats: effects on sleep and EEG.

Sleep-wakefulness and EEG responses to a chronic morphine treatment (2 mg/kg/day, IP, during 15 days) were studied in 8 cats provided with electrodes for EEG, EMG and EOG records. Results indicated that, in contrast to a resistance of the cats to exhibit overt signs of tolerance in the immediate behavioral and EEG responses to morphine, tolerance developed in sleep since: 1) there was a reduction in its onset latency after the initial insomnia period; 2) despite that the initial insomnia period was present throughout the treatment, compared to the effects of the first MS day, the total amount of both NREM sleep and REM sleep significantly increased in subsequent drug days, the total amount of REM sleep reached similar placebo values from day 5; 3) the restoration in the total amount of both sleep states was due to significant increases that occurred from day 5 after the first 6 hours of the MS injection. During the 19-24 hours after MS injections, increases of NREM and REM also resulted statistically significant compared to placebo values. A biphasic depressed and aroused response occurred during early withdrawal. REM sleep rebound was present after MS discontinuation and in the following week. Similarities with effects of opiate chronic administration in other species are discussed. These results support the potential use of the cat for the study of neural mechanisms involved in sleep chronic effects of opiates.

Animals

H-2 antigens and tumour-associated transplantation antigens in clones derived from a methylcholanthrene-induced BALB/c tumour: their influence on the generation in vitro and in vivo of the specific anti-tumour immune response.

The methylcholanthrene GR9 tumour is a fibrosarcoma, originated in a BALB/c (H-2d) mouse, composed of different clones (A7, G2, D8, D6, B11, B3, B7, C11, B10, B9) with different class I (Kd Dd Ld) expression. We present data indicating that MHC class I differences observed between the different clones correlated with RNA levels and can be modified with recombinant interferon-gamma. We also studied the presence of tumour-associated antigens in GR9 and their different clones using the monoclonal antibody (MoAb) technology. We produced two syngeneic MoAbs, A7.2 and A7.6, which reacted to GR9 clones. These MoAbs precipitated a 70-kilodalton molecule and did not react with cells positive for the classical Gp70 antigen such as YC-8, LSTRA (H-2d) and RBL-5 (H-2b) lymphomas. A7.2 and A7.6 MoAbs were also negative with normal cells. In this well-characterized tumour model, we analysed the influence of the expression of class I molecules and tumour-associated antigens upon the generation, in vitro and in vivo, of the specific anti-tumour immune response. We produced syngeneic anti-GR9 A7 cytotoxic T lymphocytes (CTLs) which showed significant cytotoxicity against most of the GR9 clones including clones with low or no H-2 class I expression. These CTLs showed no cytotoxic activity against other tumour cells and concanavalin A blasts, neither could the CTL-specific response be inhibited with A7.2 and A7.6 syngeneic MoAbs nor with a panel of anti-class I MoAbs. In vivo experiments have shown that pre-immunization with the immunogenic clone GR9 A7 protects against a challenge of the different GR9 clones, independently of their class I expression and their in vitro susceptibility to lysis by anti-GR9 A7 CTLs. These results demonstrate the existence of cross-reactive tumor-associated transplantation antigens between different clones of the same tumour and the absence of correlation between in vitro susceptibility to lysis and in vivo tumour rejection. Finally, we discuss these results in the context of anti-tumour effector mechanisms generated in chemically induced tumours.

Animals

Metergoline as an inhibitor of prolactin release.

In a randomized, double-blind study, 12 and 16 mg of metergoline and 5 mg of bromoergocriptine were given daily to three groups of 100 women each for ten consecutive days to prevent lactation. Excellent or good results were obtained in 86%, 90% and 83%, respectively. Serum prolactin (PRL) levels were evaluated in three settings. The first was after a single dose in four groups of patients (4, 6 and 8 mg of metergoline and 2.5 mg of bromoergocriptine were studied for ten hours). Second, for a study of the suckling reflex, PRL levels were measured 15, 30 and 60 minutes after breast stimulation in four groups of five patients each: two groups on the fourth postpartum day with and without metergoline treatment and two groups on the eighth postpartum day (the reflex was suppressed in the two groups treated with metergoline). Third, serum PRL levels rose after the intravenous administration of 200 mg of thyrotropin-releasing hormone (TRH) in another two groups of ten patients, one treated with metergoline and the other not so treated. TRH stimulation was not blocked in the treated groups.

Bromocriptine

Unilateral lesions in locus coeruleus area enhance paradoxical sleep.

To clarify the effect of locus coeruleus (LC) lesions in sleep mechanisms, modifications in the amount of wakefulness (W), drowsiness (D), slow sleep (SS) and paradoxical sleep (PS) were examined in 9 cats with unilateral lesions in the dorso-lateral pontine tegmentum and in 3 sham-operated controls. In 4 animals the LC area was unilaterally destroyed--affecting structures that have previously been proposed as PGO-off elements--while the remaining 5 cats had lesions situated close to but sparing the LC area. Analysis of variance among baseline values of all cats, 'postlesion' values of the sham-operated controls and the postlesion values of the 2 groups of operated animals, indicated that the variations of W, D and SS among the different groups were not statistically significant. Only variations in the time spent in PS reached statistically significant values. Individual comparisons between PS values of the 4 groups showed that only an increase of PS in the animals with lesions in the LC area was statistically significant, in comparison with the PS values of the remaining groups. These results indicate that the dorso-lateral pontine area, which is considered to exert a tonic inhibitory influence in the generation of the phasic activity during PS, also mediates in the sleep-wakefulness cycle as an inhibitory region for controlling proportions of PS.

Animals

[Management of podalic delivery].

A study has been made of obstetric assistance in 1 796 podalic version labors between 1966 and 1982, with 12.4% of cesarean sections, an extremely conservative criterion. The corrected intra-and postnatal mortalities were 141.1% and 26.6% for premature and mature deliveries respectively. 744 children were examined between 4 and 10 years after birth, using clinical studies, intelligence quotient measurements by the method of Wppsi or WISC (according to age), EEG observations if necessary and stimulatory, motor and behavioral neurological tests. The results are compared with those of a similar study using 418 control children whose cephalic version births were spontaneous and completely normal. Care should be taken in interpretation of births through the vaginal canal in order to exclude the 30%-50% of cases with a wide safety margin, in which the danger is essentially zero in mature fetuses and in premature fetuses of 2 to 2.5 kg. Cesarean section should be performed almost systematically when the fetus weighs less than 2 kg, so as to avoid any possible danger to the child.

Adult

No inhibition of corticotrophin (ACTH)-hypersecretion in adrenal insufficiency by somatostatin.

Somatostatin (250 micrograms as a bolus iv and 250 micrograms as a 1 h infusion) was administered to 6 patients with primary adrenal insufficiency (Addison's disease). The fall in plasma ACTH during the infusion period ranged between 0-30% with a mean reduction of 11.2 +/- 11.6%. These findings suggest that with the method employed, somatostatin is not an inhibitor of ACTH secretion in a condition in which glucocorticoids are lacking.

Addison Disease

Probable pituitary adenoma with adrenocorticotropin hypersecretion (corticotropinoma) secondary to Addison's disease.

A 50-yr-old woman with Addison's disease from the age of 14 yr was diagnosed as empty sella turcica in 1974 (Rev Clin Esp 139: 183, 1975). She subsequently continued with hyperpigmentation in spite of adequate hormone substitution therapy which permitted her to lead a normal life. When studied she showed an extreme elevation of plasma ACTH (1500--2000 pg/ml), and with dexamethasone (2 and 8 mg/day) continued to have levels of 900 pg/ml. With 60 mg hydrocortisone daily, effects of overdosage were observed (swelling and Cushingoid facies) associated with depigmentation. However, she continued to manifest levels of plasma ACTH of 700 pg/ml and an absence of circadian rhythm. It seems likely that this patient represents a case of pituitary ACTH secretory adenoma (corticotropinoma) secondary to the preexisting Addison's disease. The circulating levels of other pituitary hormones were normal.

Addison Disease