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Biomedical subjects

L Fernández

Publications and source records attributed to L Fernández.

At least 19 recordsLinked to original sources

Endometrial stromal sarcoma expression of estrogen receptors, progesterone receptors and estrogen-induced srp27 (24K) suggests hormone responsiveness.

The endometrial stroma plays a decisive role in sustaining the gland epithelium along the menstrual cycle, and in preparing the microenvironment that allows embryo implantation. The stroma undergoes important changes during the menstrual cycle that affects both the cell number and differentiation. These changes are regulated by both estrogen and progesterone. Stromal sarcomas are extremely rare, occurring much less than any other uterine tumor. Their origin and biology are poorly understood. The purpose of this work was to try to learn more about the stromal physiology, and also to ascertain whether the stromal sarcoma has characteristics of hormone dependence. We studied the presence of estrogen receptors (ER), progesterone receptors (PR) and the stress-responsive protein of 27K (srp27, a protein first described as an estrogen-induced 24K protein in MCF-7 cells) in both normal stroma and stromal sarcoma. The ER and PR were measured by exchange assays. The srp 27 was studied both by Western-blot and by IHC by means of specific monoclonal antibodies. The stromal sarcomas studied showed a high concentration of both ER (96 to 116 fmol/mg prot.) and PR (565 to 995 fmol/mg prot.). These amounts of ER and PR were higher than the mean found in normal endometrium during the proliferative phase (43 and 637 fmol/mg prot., respectively), and much higher than that of the secretory phase (17 and 229 fmol/mg prot., respectively). The srp27 characterized by Western-blot in both the normal stroma and stromal sarcoma was found to be similar to the srp27 of breast cancer. The IHC results showed a very low expression of srp27 in the stroma during the proliferative phase that increases when the endometrium enters the secretory phase. The low-malignancy grade stromal sarcomas showed abundant expression of srp27, but the high-malignancy grade sarcomas showed no expression of srp27. The obtained results prove the stroma capability to express the srp27. A negative correlation between malignancy of stromal tumors and srp27 expression was found. The presence of ER and PR in some stromal sarcomas proves that they have characteristics of hormone responsiveness. These findings suggest that ER and PR assays should be routinely performed in stromal sarcomas as well as in endometrial adenocarcinomas, and also that antiestrogenic drugs might be considered for the treatment of ER and PR positive stromal sarcomas.

Antineoplastic Agents

The estradiol induction of the microsomal low-affinity glucocorticoid binding sites (LAGS) in the male rat liver is independent of the endocrine status.

The low-affinity glucocorticoid binding sites (LAGS) are entities present in the microsomal fraction of the rat liver, capable of binding several glucocorticoids and progesterone with low affinity. The present work focuses on the demonstration that estradiol exerts a powerful stimulatory effect on the LAGS concentration. For this purpose, we studied the effect of this hormone in immature, hypothyroid, and hypophysectomized rats, three experimental models which present a very low level of LAGS. In all of them, estradiol showed ability to significantly increase the level of LAGS. The positive results obtained in hypophysectomized rats point to a direct action of estradiol on the liver. In immature rats, the estradiol induction of the LAGS was shown to be especially slow, 3-4 days after estradiol administration being necessary to obtain a significant rise in the level of LAGS. Moreover, the dose of estradiol necessary to obtain the LAGS induction in these rats (0.5 mg/100 g body weight) was clearly supraphysiological. From these data we concluded that: (A) estradiol is a powerful stimulator of the LAGS concentration, its effect probably being exerted directly on the liver; and (B) to elicit its effect, estradiol does not need the participation of other hormones known to be implicated in the endocrine regulation of the LAGS.

Animals

Thyroid hormones and glucocorticoids act synergistically in the regulation of the low affinity glucocorticoid binding sites in the male rat liver.

The low affinity glucocorticoid binding sites (LAGS) have been described and partially characterized in both the nuclei and microsomes of rat liver. The LAGS concentration is under endocrine regulation, as proved by their decrease after adrenalectomy and their almost complete disappearance after hypophysectomy. This article describes new data that also implicate the thyroid hormones in the endocrine regulation of LAGS. The LAGS were measured by [3H]dexamethasone exchange assay in crude microsome suspensions of rat liver. Propylthiouracil-induced hypothyroidism (TX) provoked a 90% reduction in the LAGS levels with respect to the control value. The administration of T3 to TX rats was able to completely restore the LAGS level. On the other hand, adrenalectomy (ADX) provoked a 50% decrease in LAGS levels, and this effect could be reverted by treatment with corticosterone acetate. TX rats that were also adrenalectomized (TX-ADX) showed a LAGS level similar to that of the TX rats. However, treatment of these rats with T3 was much less effective than in TX rats. A complete restoration of the LAGS level in TX-ADX rats could be achieved only with a combined treatment of corticosterone acetate plus T3. Similar results to those obtained in TX-ADX rats were also obtained in immature or hypophysectomized rats, two experimental models known to possess very low or undetectable levels of LAGS. From these findings we conclude that: 1) thyroid hormones, as well as glucocorticoids, play an important role in the regulation of the LAGS level; 2) glucocorticoids and thyroid hormones act synergistically in the endocrine regulation of LAGS; and 3) the results obtained in the hypophysectomized rats point to a direct action of glucocorticoids and T3 on the LAGS level of the rat liver.

Adrenalectomy

Thyroid hormone action on ACTH secretion.

Thyroid hormone effects on pituitary ACTH have not been well established. Adult male Sprague-Dawley rats were rendered hypo- and hyperthyroid while undergoing treatment with 6-Propylthiouracil (PTU) and L-Thyroxine (T4). At the time of decapitation, plasma values for T4 (micrograms/100 ml) were 3.9 +/- 0.4 in the control, 17.3 +/- 2.2 in the T4 and less than 2 in the PTU treated group; plasma T3 and TSH confirmed hyper- and hypothyroidism in the T4 and PTU treated groups respectively. Plasma immunoassayable ACTH and corticosterone were significantly increased in hyperthyroid and decreased in the PTU treated animals. Pituitaries were removed and incubated in DMEM. After 3 h incubation, ACTH content and secretion to the medium were significantly lower in the PTU group. As expected, pituitary TSH content and secretion were decreased in the T4 treated animals. These data indicate that thyroid hormones influence pituitary-adrenal function by increasing ACTH secretion and consequently corticosterone production.

Adrenocorticotropic Hormone

Antiphospholipid antibodies and the antiphospholipid syndrome in systemic lupus erythematosus. A prospective analysis of 500 consecutive patients.

Five hundred consecutive patients with systemic lupus erythematosus (SLE) were entered into a prospective study of anticardiolipin antibodies (ACLA) in their 3 major immunoglobulin isotypes and followed thereafter with repeated testing for a mean period of nearly 8 months. Manifestations of SLE that were strongly associated with ACLA included venous thrombosis (particularly when recurrent), thrombocytopenia, hemolytic anemia, recurrent fetal loss, and leg ulcers. Other manifestations found to be associated with ACLA were arterial occlusions, transverse myelitis, and pulmonary hypertension. Conversely, we found no relationship between ACLA and migraine, convulsions, transient ischemic attacks, psychoses, or avascular necrosis of bone. No relationship was found between the presence of ACLA and that of anti-DNA antibodies studied in the same serum sample. Association with ACLA grew stronger and titers became higher in patients with several of the associated manifestations. Statistical analyses revealed the existence of a syndrome, the antiphospholipid syndrome, comprising 2 or more manifestations in conjunction with ACLA titers 5 standard deviations above the mean of normal control subjects, particularly if ACLA had been positive on at least 2 occasions. We propose that such criteria could be applied to the definition of the antiphospholipid syndrome. The presence and the titers of these antibodies related to disease activity and titer decreased by treatment, particularly when they were of the IgM isotype. Patients in whom a thrombotic episode occurred during the course of the study were observed to have a coincident decrease in ACLA titers, a finding that might indicate consumption of the antibody during the event. Treatment and the resulting inactivation of disease appear to have independent effects on ACLA titers. Physicians should therefore be cautious in prescribing high doses of corticosteroids or immunosuppressants to patients with SLE solely because they have high titers of ACLA.

Abortion, Spontaneous

[Peritoneal hydatidosis with fistulization into the sigmoid colon].

A case is presented of peritoneal hydatidosis with fistulization into the sigmoid in a patient who had previously undergone surgery for hepatic hydatidosis. The clinical picture made its debut as an alteration in intestinal habit followed by the appearance of diarrheic syndrome and expulsion of hydatid membranes. The natural history of peritoneal hydatidosis, its complications and therapeutic guidelines are discussed.

Aged

[Histiocytosis X: localized and disseminated forms. Apropos of 13 cases].

The authors present a study of 13 patients, between 7 months and 4 years of age diagnosed, of histiocytosis X, nine of them with a disseminated form and 4 with a localized form. The clinical and histopathologic types of presentation are analyzed, applying the usual scores of prognostic evaluation, with emphasis on the low mortality rate (one death), considering that there are several patients with bad prognostic scores. This is explained by the positive effect of chemotherapy used in these cases.

Antineoplastic Combined Chemotherapy Protocols

Risk factors in mass screening for breast cancer, multivariate analysis of data from the Cuban diagnosis pilot study.

The evolution of mammography has provided possibilities for mass screening programs. Early diagnosis is considered the most important factor in reducing the breast cancer mortality but the mass screening is very expensive if we include all female population. In this paper we show the results of an early diagnosis pilot study with a multivariate data analysis. Data concerning risk factors (age, age at menarche, menopause, parity, age at first childbirth, lactation, abortions and previous benign breast disease) were recorded in 438 patients with breast carcinoma and 1750 patients with benign breast diseases diagnosed in the Early Diagnosis Pilot Program at the National Institute of Oncology and Radiobiology in Cuba. A group of 449 healthy women living in Havana City was also studied. Age and age at first childbirth were the major factor considered. Multivariate data analysis allowed to build stratification trees identifying subgroups with different breast cancer incidence. The usefulness of these stratifications for screening with optimal coverage, sufficiency and efficacy, is discussed.

Adult

Alterations in thrombopoiesis in patients with thrombocytopenia produced by dengue hemorrhagic fever.

The causes of thrombocytopenia, one of the most dangerous symptoms in the course of dengue hemorrhagic fever (DHF), are not yet clear. We studied patients with DHF (dengue virus type 2), grouped according to days of illness, platelet counts, serum thrombopoietin (Tpo) levels, and bone marrow differential counts. During the thrombocytopenic phase of disease (3rd-8th days) the Tpo levels were not increased in spite of low platelet counts. Beginning from the 6th-7th day in some patients, a rapid increase in Tpo levels was observed, followed by a rise in the platelet counts. By the 9th-11th days all patients studied were in this phase of convalescence. The bone marrow specimens obtained on the 6th-10th days of illness showed a megakaryocytic hyperplasia in 60% of cases. It seems that dengue viruses provoke a transitory alteration in the humoral regulation of thrombopoiesis which possibly may be the consequence of the lymphoid tissue damage. This extends the thrombocytopenic state and contributes to the appearance of hemorrhagic complications.

Adult