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Biomedical subjects

D Miranda

Publications and source records attributed to D Miranda.

At least 37 records · Page 2Linked to original sources
PubMed1995

Studies of natural killer cell activity in a drug-free, healthy population. Response to a challenge with taxol, estramustine and lipopolysaccharide.

Preincubation of peripheral blood lymphocytes with the microtubule disturbing agents estramustine (ETMN; n = 7, final conc. 20 microM) or taxol (TX; n = 13, final conc. 10 microM), resulted in a statistically significant inhibition of natural killer cell activity [(NKCA); baseline (x +/- SD; expressed as percentage of specific chromium release) of 32.2 +/- 30.5 and 34.4 +/- 27.7 and drug treated samples of 13.9 +/- 19.9 and 12.5 +/- 20.8, respectively; Student's paired t-test p < 0.005]. Furthermore, most individual values for NKCA in the drug preincubated samples were at least 20% below the same subject baseline lytic function (except for TX sample No.1), and NKCA was non detectable in 4 out of 7 and 5 out of 13 samples (pretreatment with either ETMN or TX< respectively). The use of other concentrations and different preincubation times for these chemotherapeutic agents also produced NKCA inhibition, which was time and dose dependent. Preincubation with lipopolysaccharide (LPS; n = 16, final conc. 50 micrograms/ml), an endotoxin prominently involved in the etiology of septic shock, resulted in a statistically significant enhancement of NKCA [baseline (x +/- SD; expressed as percentage of specific chromium release) of 25.4 +/- 20.4 and LPS treated sample of 36.6 +/- 17.4, respectively; Student's t paired t-test p < 0.005]. At least a 20% increase in NKC lytic function over its own baseline value was recorded for each and everyone of the samples tested with LPS.2+ the pathophysiology associated with septic shock.

Adult↗
PubMed1994

Dietary nucleotides: effects on the gastrointestinal system in swine.

Nucleotides in the intestinal lumen may decrease the inflammatory response to ischemia-reperfusion. In a newborn-swine model, we showed that perfusion of the intestinal lumen with nucleotides in concentrations similar to those in human milk induced hyperemia. The levels of hypoxanthine (and xanthine) were not increased in the presence of nucleotides during ischemia-reperfusion, and the number of leukocytes accumulated in the intestine was reduced in the presence of nucleotides. Furthermore, nucleotides may have decreased protein leak and the production of nitric oxide during ischemia. These effects are not changed significantly in the presence of an adenosine antagonist. We interpreted our results to indicate that the protective effects of nucleotides in the intestinal lumen are not due to adenosine alone.

Adenosine↗
PubMed1994

[Natural killer cytolytic activity in renal and prostatic cancer].

Natural killer cytolytic activity, the basis of cancer immunotherapy that uses cytolytic cells, may be impaired in cancer. The aim of this work was to study in vitro the natural killer cytolytic activity and its response to the immunomodulators interleukin-2, interferon and phytohemagglutinin stimulated lymphocyte proliferation in a group of 9 patients with renal cell cancer and 6 with prostatic cancer. The results were compared with those of 20 normal volunteers. Twelve patients were operated and were studied twice 48 h and 14 days after surgery. Natural killer cytolytic activity was significantly lower in renal cell and prostatic cancer patients than controls (3.3 +/- 1.6, 4.9 +/- 2.2 and 20.6 +/- 3.7% of specific lysis respectively). This activity was not modified in cancer patients by interleukin-2 50 UI/ml or interferon 3000 UI/ml and did not differ in the two postoperative periods. Phytohemagglutinin stimulated lymphocyte proliferation was also lower in cancer patients, compared to controls (stimulation index of 18 +/- 3 and 26.5 +/- 5 respectively). It is concluded that these patients have a low immunological level and that this study is the first step towards an immunological characterization of cancer patients that are candidate to adoptive immunotherapy.

Adult↗
PubMed1994

Enhancement of natural killer cell activity in septic shock patients by a mixture of the calcium ionophore A23187 and the phorbol ester TPA: in vitro studies.

Preincubation of peripheral blood lymphocytes from drug-free, healthy volunteers with a mixture of the calcium ionophore A23187 (Io) and the phorbol ester TPA (12-O-tetradecanoylphorbol-13-acetate) consistently resulted in a significant enhancement (dose-dependent; maximum immunostimulation obtained with the Io + TPA final mixture concentration of 10 uM + 250 ng/ml, respectively) of natural killer cell activity (NKCA) (n = 8; mean +/- SD of 16.8 +/- 8.9 and 52.0 +/- 18.0, paired Student's t-test p < 0.005; effector-to-target cell ratio of 30:1). Results from the same protocol, but using samples from septic shock patients followed a similar trend; however, and perhaps reflecting the significantly lower baseline NKCA in this group of individuals (n = 7), the mean value reached for this cellular immune function after incubation with Io + TPA was significantly lower than that of the treated controls' group (mean +/- SD of 19.8 +/- 11.6 and 52.0 +/- 18.0, respectively, Student's t-test p < 0.005). As expected from the role of calcium in the activation of NKCA, incubation with the Io significantly increased baseline NKCA, which was largely unchanged by TPA. Expression of the CD56+ and CD16+ phenotypes in septic shock patients did not correlate directly with NKCA, suggesting that this condition may be associated with changes in the function rather than the quantity of these cellular markers.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

In vitro studies of natural killer cell activity in septic shock patients. Response to a challenge with alpha-interferon and interleukin-2.

Natural killer cell activity (NKCA) in patients with septic shock was statistically significantly lower than the value recorded for a group of drug-free, healthy volunteers [9.1 +/- 7.8 (n = 20) and 20.6 +/- 16.6 (n = 15), respectively; Student's test, p < 0.05]. As expected, preincubation of peripheral blood lymphocytes from samples taken from a group of controls with either alpha-interferon or interleukin -2 resulted in an enhancement of NKCA for each and everyone of the subjects studied; however, results from a similar protocol using patient samples showed a lack of consistency, both in the direction and magnitude, in the elicited changes in NK lytic function. Whereas samples from same patient responded with either an increase or a decrease in NKCA to preincubation with both immunostimulators, others responded with NKCA upmodulation to one and downmodulation to other of these test substances. A better knowledge of the mechanism(s) responsible for the depressed expression of NKCA in septic shock patients, and its altered response to alpha-interferon and interleukin-2, could generate new modalities in the diagnosis and therapy of this condition.

Adult↗
PubMed1992

Enhancement of human natural killer cell activity by opioid peptides: similar response to methionine-enkephalin and beta-endorphin.

We studied the effect of methionine-enkephalin (MET) and beta-endorphin upon human peripheral blood lymphocyte natural killer cell (NKC) activity in a group of healthy volunteers (n = 27; 17 male and 10 female, age +/- SD and range of 32 +/- 6, 25-43 years and 36 +/- 11, 22-65 years, respectively). Aliquots from some individual samples were preincubated separately with different concentrations of either peptide (n = 12), while others were tested with only one of these substances (MET, n = 6; beta-endorphin, n = 9). Using each individual as its own control, MET (10(-8) and 10(-6) M) and beta-endorphin (10(-10) and 10(-8) M) significantly increased NKC activity (NKCA) (at least 20% over base value, effector-to-target cell ratio, 40:1) in 7 out of 15 and 7 out of 19 subjects, respectively. Results obtained from the rest of the samples were mixed, e.g., changes observed in NKCA were not significant or showed significance with only one of the peptide concentrations studied. Cells from individuals showing a significant increase in NKC lytic function following preincubation with either MET or beta-endorphin responded similarly to the other peptide (in both cases 5 out of 6 subjects), suggesting that enhancement of NKCA by MET and beta-endorphin may work through a similar mechanism.

Adjuvants, Immunologic↗
PubMed1991

[Immunological defects in septic shock. Deficiency of natural Killer cells and T-lymphocytes].

It is well known that an immunosuppressive response occurs after acute trauma. Some cellular mediators participate in the pathogenesis of septic shock. However, the exact role of the lymphocyte subsets and natural killer (NK) activity in this condition is not clear. We studied NK cytolytic activity through a 51Cr liberation assay using K-562 target cells in 20 patients with initial septic shock (10 men and 10 females, mean age 41 years old). Lymphocyte subsets CD3 (T3), CD4 (T4), CD8 (T8), CD16 (Leu-11) and CD56 (Leu-19) were also studied by indirect immunofluorescence. Compared to results obtained in 20 healthy volunteers, patient's NK activity was decreased (4.6 +/- 3.9 vs 26.1 +/- 10, p less than 0.025), CD16 was lower (10%/187 vs 15%/280 per ul) and CD56 was also lower (6%/120 vs 12%/224 per ul), p less than 0.05. T lymphocyte subsets were also decreased: CD3 cells (1100 vs 1352 per ul) and CD4 cells (634 vs 873 per ul), p less than 0.05. Thus, a severe decrease in NK cells and NK cell function as well as decreases in CD3 and CD4 lymphocyte subsets are present in the initial stages of septic shock. The predictive value of these findings is currently under study.

Adolescent↗
PubMed1990

Retinoic acid inhibition of human breast carcinoma proliferation is accompanied by inhibition of the synthesis of a Mr 39,000 protein.

Retinoic acid (RA) inhibits proliferation of numerous breast carcinoma cells and prevents estrogen stimulation of growth of several estrogen receptor (ER)-positive cell lines. RA inhibition of human breast carcinoma cell proliferation is associated with marked inhibition of the synthesis of a Mr 39,000 protein in the ER-positive human breast carcinoma cell lines investigated. Inhibition of the synthesis of the Mr 39,000 protein occurred within 24 h of RA addition and coincides with the onset of inhibition of cellular proliferation. Increasing the dose of RA results in increasing inhibition of Mr 39,000 synthesis. RA does not inhibit the proliferation of the ER-negative human breast carcinoma cell line MDA MB-231; synthesis and inhibition of the Mr 39,000 protein is not noted in this cell line. Tamoxifen, which inhibits ER-positive breast carcinoma proliferation, moderately inhibits Mr 39,000 synthesis, while a concentration of difluoromethylornithine which inhibits cellular proliferation by greater than 50% does not affect Mr 39,000 protein synthesis. Thus, inhibition of the Mr 39,000 protein appears not to be simply related to the cessation of cellular proliferation.

Breast Neoplasms↗
PubMed1990

Retinoid modulation of estradiol-stimulated growth and of protein synthesis and secretion in human breast carcinoma cells.

All-trans-retinoic acid (RA) has been demonstrated to inhibit the growth of numerous breast carcinoma cell lines. In this study we demonstrated that RA inhibits estradiol stimulation of proliferation of the estrogen-dependent breast carcinoma cell lines MCF-7 and ZR-75. RA inhibition of MCF-7 breast carcinoma cell proliferation is associated with the marked stimulation of the synthesis and secretion of a 75,000 molecular weight protein. Minor stimulation of the synthesis and secretion of other proteins was also noted, including 160,000, 95,000, 89,000, 82,000, 52,000 and 46,000 molecular weight proteins. Increased synthesis and secretion of the Mr 75,000 protein was noted with as little as 10 nM RA. Stimulation of the synthesis and secretion of this protein occurred within 24 h of adding the retinoid and at the time of RA inhibition of cellular proliferation. RA stimulated the production and secretion of this protein both in the absence and presence of estradiol. Stimulation of the secretion and synthesis was not noted in the presence of difluoromethyl-ornithine or tamoxifen, both of which significantly inhibited cellular proliferation. The estrogen-dependent breast carcinoma cell line ZR-75 when exposed to RA also expressed increased synthesis of the Mr 75,000 and 46,000 proteins but increased synthesis was not noted in the RA-resistant cell line MDA-MB-231. Stimulation of the synthesis and secretion of the Mr 75,000 and/or 46,000 proteins may be intimately involved in RA inhibition of cellular proliferation.

Breast Neoplasms↗
PubMed1989

Secretory character of a group of isoproterenol-induced polypeptides in mouse parotid glands.

The secretory nature of the isoproterenol-induced mouse parotid polypeptides C, D, E, F, and G (molecular weights 64,000, 61,000, 51,500, 38,000, and 37,000, respectively) is documented. Polypeptides C, D, E, F, and G, accumulated in response to successive daily stimulations with isoproterenol, were detected in a fraction enriched in hypertrophic parotid acinar cells. These cells, characterized by an increased content of cytoplasmic granules, maintain a secretory responsiveness to isoproterenol, which has been evidenced by light microscopy, enzymatic analysis, and unidimensional SDS-polyacrylamide gel electrophoresis. Thus, a parallelism in the loss and recovery of both secretory granules, alpha-amylase and polypeptides C, D, E, F, and G, was observed. Moreover, after secretion stimulation, polypeptides C, D, E, F, and G were detected in the fluid collected directly from parotid gland cannulation. Given the secretory character of polypeptides C, D, E, F, and G, mechanisms explaining both their progressive accumulation along the chronic administration of isoproterenol, as well as their progressive disappearance observed after suspending that treatment, are discussed.

Animals↗
PubMed1987

Changes in the polypeptide composition related to the growth response in chronically isoproterenol-stimulated mouse parotid glands.

The administration of isoproterenol induces DNA-synthesis mitosis and growth (increase in size) responses in mouse parotid glands. Both responses were uncoupled by means of daily stimulations with isoproterenol in such a way that the DNA-synthesis mitosis response was observed during the first 4 days only, whereas the growth response was continuous since the first stimulation until about day 12. In parallel to the chronic stimulation by isoproterenol, drastic changes in the polypeptide composition of parotid glands were observed. These modifications, consisting basically of the reduction in content of a couple of major poly peptides (polypeptides A and B) together with the reciprocal massive accumulation of five new polypeptides (polypeptides C, D, E, F and G), were also progressive and continuous along the chronic stimulation by isoproterenol, even after the disappearance of the DNA-synthesis mitosis response. Thus, a relationship between specific changes in the mouse parotid content of polypeptides A, B, C, D, E, F and G and the isoproterenol-induced growth response, rather than with the DNA-synthesis mitosis response, is suggested. The correlation is firmly supported by the progressive recovery of the normal polypeptide composition upon suspending isoproterenol treatment, which allows parotid glands to return to normal size parameters.

Animals↗
PubMed1986

Correlation between the induction of leukemic cell differentiation by various retinoids and modulation of protein kinases.

During retinoic acid induced differentiation of the human promyelocyte leukemia cell line HL60 and the human myeloblast cell line RDFD along the myeloid pathway, there is marked modulation of both the cyclic adenosine 3':5'-monophosphate dependent protein kinase and the phospholipid-sensitive calcium dependent protein kinase. In order to further assess whether these kinases are intimately associated with the differentiation process, we have correlated the modulation of these enzymes and phosphorylations of their substrates with the extent of differentiation induced by various retinoid derivatives. We observed that there was a direct relationship between the degree of differentiation of the two leukemic cell lines and the elevation of the cyclic adenosine 3':5'-monophosphate dependent protein kinase and phospholipid sensitive calcium dependent protein kinase activities. In addition, the increased phosphorylation of the various substrates of these enzymes also correlates with the degree of differentiation. These observations support the hypothesis that modulation of these protein kinases and phosphorylation of their substrates are necessary steps in the differentiation process.

Cell Differentiation↗
PubMed1985

Renal cortical necrosis following Bothrops jararaca and B. jararacussu snake bite.

Out of 22 patients admitted to the Intensive Care Unit of the Hospital das Clínicas, Federal University of Minas Gerais, with acute renal failure following Bothrops snake bite, 7 had renal cortical necrosis. This complication was suspected when the oligoanuric phase ranged from 21 to 28 days or when the patient, in spite of having a polyuric phase, maintained elevated blood levels of urea and creatinine after the interruption of the dialysis program, and was confirmed by a kidney biopsy. Three patients died and in two of them renal cortical necrosis was found at necropsy. Four patients were discharged from the hospital and follow-up was possible in two of them who showed recovery of renal function. Vasospasm, direct nephrotoxicity of Bothrops venom and/or disseminated intravascular coagulation leading to vascular occlusion and renal ischemia are the proposed pathogenetic mechanisms to explain renal cortical necrosis following Bothrops snake bite.

Acute Kidney Injury↗
PubMed1983

Phaeohyphomycotic cyst: a clinicopathologic study of the first four cases described from Brazil.

Four cases of phaeohyphomycosis in the form of chronic and isolated cysts are presented. The cysts were strictly confined to the subcutaneous tissue, with no involvement of the corresponding skin. Patients were asymptomatic, without satellite lesions or regional lymphadenopathy. The clinicopathologic importance of this type of phaeohyphomycosis is discussed. As far as we know, our cases are the first described from Brazil.

Aged↗
PubMed1982

A new hygroscopic condenser humidifier.

A new hygroscopic condenser humidifier for the mechanically ventilated patient has been tested. It functions as a heat and moisture exchange device (HME) with an additional hygroscopic sponge to minimize the water loss from the breathing circuit. A comparative in vitro study was undertaken with a conventional HME. The influence of tidal volume, inspiratory flow rate and minute volume on the relative humidity of the inspiratory gas and on the water loss was investigated. The new device provides adequate humidification within a broad scale of ventilatory settings. In a subsequent clinical test the hygroscopic condenser humidifier proved to be a simple and reliable way of humidification.

Humans↗